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Aim: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults., Methods: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis., Results: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups., Conclusions: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562., (© 2024 Japan Geriatrics Society.)

Abstract: Roberts, BM, Staab, JS, Caldwell, AR, Sczuroski, CE, Staab, JE, Lutz, LJ, Reynoso, M, Geddis, AV, Taylor, KM, Guerriere, KI, Walker, LA, Hughes, JM, and Foulis, SA. Sex does not affect changes in body composition and insulin-like growth factor-I during US Army basic combat training. J Strength Cond Res 38(6): e304-e309, 2024-Insulin-like growth factor 1 (IGF-I) has been implicated as a biomarker of health and body composition. However, whether changes in body composition are associated with changes in IGF-I is unclear. Therefore, we examined the relationship between body composition changes (i.e., fat mass and lean mass) and total serum IGF-I levels in a large cohort of young men ( n = 809) and women ( n = 397) attending US Army basic combat training (BCT). We measured body composition using dual energy x-ray absorptiometry and total serum IGF-I levels during week 1 and week 9 of BCT. We found that pre-BCT lean mass ( r = 0.0504, p = 0.082) and fat mass ( r = 0.0458, p = 0.082) were not associated with pre-BCT IGF-I. Body mass, body mass index, body fat percentage, and fat mass decreased, and lean mass increased during BCT (all p < 0.001). Mean (± SD ) IGF-I increased from pre-BCT (176 ± 50 ng·ml -1 ) to post-BCT (200 ± 50 ng·ml -1 , p < 0.001). Inspection of the partial correlations indicated that even when considering the unique contributions of other variables, increases in IGF-I during BCT were associated with both increased lean mass ( r = 0.0769, p = 0.023) and increased fat mass ( r = 0.1055, p < 0.001) with no sex differences. Taken together, our data suggest that although changes in IGF-I weakly correlated with changes in body composition, IGF-I, in isolation, is not an adequate biomarker for predicting changes in body composition during BCT in US Army trainees., (Copyright © 2024 National Strength and Conditioning Association.)

In this study, an insulin-like growth factor-1 (IGF-1) certified reference material (CRM) was developed by the National Institute of Metrology (NIM), and two different principles for evaluating the IGF-1 CRM were established. After optimisation of the acid hydrolysis conditions (110 °C, 36 h), quantitative determination of peptide purity, and chromatographic separation and mass spectrometric detection, amino acid analysis-based high-performance liquid chromatography combined with isotope-dilution tandem mass spectrometry (AAA-HPLC-IDMS/MS) and peptide analysis-based HPLC-IDMS/MS (Peptide-HPLC-IDMS/MS) were used for certified value assignment; the results obtained were 136.28 and 135.01 μg/g, respectively, which were in good agreement. These results were subjected to the normal distribution test, outlier test, and method consistency test. The homogeneity and stability of the reference materials were also examined, and the uncertainty introduced in the experimental process was calculated. The final certified value was (136 ± 15) μg g -1 (k = 2). The CRM was found to be stable for at least six months when stored at -70 °C and for 7 d when stored at higher temperatures (-20 °C, 4 °C, 25 °C, or 40 °C). The CRM is expected to be used as a primary calibrator for quality control in biopharmaceutical production and clinical diagnostics., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Youxun Jin reports financial support was provided by the National Key R&D Program of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood., Study Design: A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24 months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2 years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1])., Results: After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6 months and continued through 12-24 months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12 months, and a lower mean IGF-1 levels at birth and 6 months., Conclusion: This study demonstrates a delayed impact of PAE on growth that manifested around 6 months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay., Competing Interests: Declaration of Competing Interest Authors have indicated they have no conflicts of interest other incentives relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent years, invertebrate animals with clear genetic background and completed genome sequence have become very popular in biological research. Insulin and insulin-like peptides (ILPs) are a class of peptides having important physiological functions, including promotion of cell proliferation and differentiation, and body growth and development. To date, many invertebrates have been identified with multiple ILP families, whose structures and functions have become increasingly clear to scientists. This review summarizes the ILPs identified in the model Lepidopteran insect Bombyx mori, in the aspects of structures and classification, functions and pathways. A brief discussion on the ILPs from several other model insects, including Drosophila melanogaster, Aedes aegypti, and Apis mellifera, was also included.

Insulin‐like peptides (ILPs) belong to the insulin superfamily and act as hormones, neuromediators, and growth factors during the post‐embryonic life‐cycle stages of insects. These peptides are encoded by different genes in various species. In the genus Drosophila, eight peptides are known, seven of which are likely to bind the Drosophila insulin receptor, whereas DILP8 is a known ligand of the Lgr3 receptor. Binding of DILPs 1‐7 to receptors leads to activation of intracellular proteins related to the conserved insulin/IGF (insulin‐like growth factors) signaling pathway. The insulin pathway acts within a complex physiological regulatory network involved in the coordination of development, growth, behavior, metabolism, lifespan, and cognitive functions in insects. The current review summarizes recent data about the structure and function of ILPs in fruit flies. The role of environmental factors and genetic manipulations in modulating the functions of DILPs and their association with lifespan and metabolism of Drosophila are assessed. Further investigation and identification of pharmacological or biotechnological interventions that may decrease insulin/IGF signaling could be a highly promising approach for extension of human health span and longevity. [ABSTRACT FROM AUTHOR]

The coordination between the animal's external environment and internal state requires constant modulation by chemicals known as neuromodulators. Neuromodulators, such as biogenic amines, neuropeptides and cytokines, promote organismal homeostasis. Over the past several decades, Caenorhabditiselegans has grown into a powerful model organism that allows the elucidation of the mechanisms of action of neuromodulators that are conserved across species. In this perspective, we highlight a collection of articles in this issue that describe how neuromodulators optimize C. elegans survival. [ABSTRACT FROM AUTHOR]

Insulin-like peptides are a group of hormones crucial for regulating metabolism, growth, and development in animals. Invertebrates, such as C. elegans , have been instrumental in understanding the molecular mechanisms of insulin-like peptides. Here, we review the 40 insulin-like peptide genes encoded in the C. elegans genome. Despite the large number, there is only one C. elegans insulin-like peptide receptor, called DAF-2. The insulin and insulin-like growth factor signaling (IIS) pathway is evolutionarily conserved from worms to humans. Thus C. elegans provides an excellent model to understand how these insulin-like peptides function. C. elegans is unique in that it possesses insulin-like peptides that have antagonistic properties, unlike all human insulin-like peptides, which are agonists. This review provides an overview of the current literature on C. elegans insulin-like peptide structures, processing, tissue localization, and regulation. We will also provide examples of insulin-like peptide signaling in C. elegans during growth, development, germline development, learning/memory, and longevity. [ABSTRACT FROM AUTHOR]

Insulin signaling is a conserved pathway in all metazoans. This pathway contributed toward primordial metazoans responding to a greater diversity of environmental signals by modulating nutritional storage, reproduction, and longevity. Most of our knowledge of insulin signaling in insects comes from the vinegar fly, Drosophila melanogaster, where it has been extensively studied and shown to control several physiological processes. Mosquitoes are the most important vectors of human disease in the world and their control constitutes a significant area of research. Recent studies have shown the importance of insulin signaling in multiple physiological processes such as reproduction, innate immunity, lifespan, and vectorial capacity in mosquitoes. Although insulin-like peptides have been identified and functionally characterized from many mosquito species, a comprehensive review of this pathway in mosquitoes is needed. To fill this gap, our review provides up-to-date knowledge of this subfield.

Prostate cancer is the second most commonly diagnosed cancer in men. The mammalian insulin-like growth factor (IGF) family is made up of three ligands (IGF-I, IGF-II, and insulin), three receptors (IGF-I receptor (IGF-1R), insulin receptor (IR), and IGF-II receptor (IGF-2R)), and six IGF-binding proteins (IGFBPs). IGF-I and IGF-II were identified as potent mitogens and were previously associated with an increased risk of cancer development including prostate cancer. Several reports showed controversy about the expression of the IGF family and their connection to prostate cancer risk due to the high degree of heterogeneity among prostate tumors, sampling bias, and evaluation techniques. Despite that, it is clear that several IGF family members play a role in prostate cancer development, metastasis, and androgen-independent progression. In this review, we aim to expand our understanding of prostate tumorigenesis and regulation through the IGF system. Further understanding of the role of IGF signaling in PCa shows promise and needs to be considered in the context of a comprehensive treatment strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elemam, Hotait, Saleh, El-Huneidi and Talaat.)

Background: Optimal size at birth dictates perinatal survival and long-term risk of developing common disorders such as obesity, type 2 diabetes and cardiovascular disease. The imprinted Grb10 gene encodes a signalling adaptor protein capable of inhibiting receptor tyrosine kinases, including the insulin receptor (Insr) and insulin-like growth factor type 1 receptor (Igf1r). Grb10 restricts fetal growth such that Grb10 knockout (KO) mice are at birth some 25-35% larger than wild type. Using a mouse genetic approach, we test the widely held assumption that Grb10 influences growth through interaction with Igf1r, which has a highly conserved growth promoting role., Results: Should Grb10 interact with Igf1r to regulate growth Grb10:Igf1r double mutant mice should be indistinguishable from Igf1r KO single mutants, which are around half normal size at birth. Instead, Grb10:Igf1r double mutants were intermediate in size between Grb10 KO and Igf1r KO single mutants, indicating additive effects of the two signalling proteins having opposite actions in separate pathways. Some organs examined followed a similar pattern, though Grb10 KO neonates exhibited sparing of the brain and kidneys, whereas the influence of Igf1r extended to all organs. An interaction between Grb10 and Insr was similarly investigated. While there was no general evidence for a major interaction for fetal growth regulation, the liver was an exception. The liver in Grb10 KO mutants was disproportionately overgrown with evidence of excess lipid storage in hepatocytes, whereas Grb10:Insr double mutants were indistinguishable from Insr single mutants or wild types., Conclusions: Grb10 acts largely independently of Igf1r or Insr to control fetal growth and has a more variable influence on individual organs. Only the disproportionate overgrowth and excess lipid storage seen in the Grb10 KO neonatal liver can be explained through an interaction between Grb10 and the Insr. Our findings are important for understanding how positive and negative influences on fetal growth dictate size and tissue proportions at birth., (© 2024. The Author(s).)

Lipids are essential in insects and play pleiotropic roles in energy storage, serving as a fuel for energy-driven processes such as reproduction, growth, development, locomotion, flight, starvation response, and diapause induction, maintenance, and termination. Lipids also play fundamental roles in signal transduction, hormone synthesis, forming components of the cell membrane, and thus are essential for maintenance of normal life functions. In insects, the neuroendocrine system serves as a master regulator of most life activities, including growth and development. It is thus important to pay particular attention to the regulation of lipid metabolism through the endocrine system, especially when considering the involvement of peptide hormones in the processes of lipogenesis and lipolysis. In insects, there are several lipogenic and lipolytic hormones that are involved in lipid metabolism such as insulin-like peptides (ILPs), adipokinetic hormone (AKH), 20-hydroxyecdysone (20-HE), juvenile hormone (JH), and serotonin. Other neuropeptides such as diapause hormone-pheromone biosynthesis activating neuropeptide (DH-PBAN), CCHamide-2, short neuropeptide F, and the cytokines Unpaired 1 and 2 may play a role in inducing lipogenesis. On the other hand, neuropeptides such as neuropeptide F, allatostatin-A, corazonin, leukokinin, tachykinins, limostatins, and insulin-like growth factor (ILP6) stimulate lipolysis. This chapter briefly discusses the current knowledge of the endocrine regulation of lipid metabolism in insects that could be utilized to reveal differences between insects and mammalian lipid metabolism which may help understand human diseases associated with dysregulation of lipid metabolism. Physiological similarities of insects to mammals make them valuable model systems for studying human diseases characterized by disrupted lipid metabolism, including conditions like diabetes, obesity, arteriosclerosis, and various metabolic syndromes., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Alzheimer's disease (AD) is characterized by the deposition in the brain of senile plaques composed of amyloid-β peptides (Aβs) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE), has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 for 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1, and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme, was also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

Background: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life., Methods: First, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days. Next, preterm pigs were treated with recombinant human IGF-1 for 19 days (2.25 mg/kg/day, systemically)., Results: Relative to term pigs, preterm pigs had lower body weight, fat, bone contents, relative weights of liver and spleen and a longer and thinner intestine at 19 days. Preterm birth reduced intestinal villi heights and peptidase activities, but only at 5 and 9 days. In preterm pigs, IGF-1 reduced mortality primarily occurring from gastrointestinal complications and with a tendency towards salvaging smaller pigs. IGF-1 supplementation also increased spleen and kidney weights, small intestine length and maltase to lactase activity, reflecting gut maturation., Conclusion: Preterm birth affects body composition and gut maturation in the first 1-2 weeks, but differences are marginal thereafter. Supplemental IGF-1 may improve gut health in pigs and infants in the first few weeks after preterm birth., Impact: Insulin-like growth factor 1 (IGF-1) supplementation may improve gut health and development in prematurity, but whether the effects are sustained beyond the immediate postnatal period is unclear. In preterm pigs, the prematurity effects on IGF-1 and gut health deficiencies are most pronounced during the first week of life and diminishes thereafter. In preterm pigs, IGF-1 supplementation beyond the first week of life reduced mortality. The present study provides evidence of a sustained effect of IGF-1 supplementation on the gastrointestinal tract after the immediate postnatal period., (© 2023. The Author(s).)

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

The insulin-like growth factor (IGF) system has paracrine and endocrine roles in the central nervous system. There is evidence that IGF signalling pathways have roles in the pathophysiology of neurodegenerative disease. This review focusses on Alzheimer's disease and Parkinson's disease, the two most common neurodegenerative disorders that are increasing in prevalence globally in relation to the aging population and the increasing prevalence of obesity and type 2 diabetes. Rodent models used in the study of the molecular pathways involved in neurodegeneration are described. However, currently, no animal model fully replicates these diseases. Mice with triple mutations in APP , PSEN and MAPT show promise as models for the testing of novel Alzheimer's therapies. While a causal relationship is not proven, the fact that age, obesity and T2D are risk factors in both strengthens the case for the involvement of the IGF system in these disorders. The IGF system is an attractive target for new approaches to management; however, there are gaps in our understanding that first need to be addressed. These include a focus beyond IGF-I on other members of the IGF system, including IGF-II, IGF-binding proteins and the type 2 IGF receptor.

Background and Objective: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls., Methods: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls., Results: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls., Conclusion: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yaghoobpoor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fluoroquinolones (FQs), commonly known for their antibiotic properties, exhibit additional pharmacological potential with anti-proliferative effects on various malignant cell types and immunomodulatory responses. Despite these observed effects, the precise mechanisms of action remain elusive. This study elucidates the biological impact of FQs on insulin-like growth factor-binding protein 3 (IGFBP-3) productions in a p53-dependent manner. Cultured cells and mouse models treated with FQs demonstrated increased IGFBP-3 mRNA expression and protein secretion. The FQ-induced IGFBP-3 was identified to impede cell growth by inhibiting IGF-I signaling and exerting effects through an IGF-independent pathway. Notably, FQ-mediated suppression of cell proliferation was reversed in p53-null and p53 knockdown cells, suggesting the pivotal role of p53 in FQ-induced IGFBP-3 production and IGFBP-3-mediated growth inhibition. Additionally, ciprofloxacin, a clinically used FQ, exhibited the induction of tumor cell apoptosis and attenuation of tumor growth in a syngeneic mouse hepatocellular carcinoma (HCC) model. These findings unveil a novel mechanism through which FQs act as anti-proliferative agents, prompting further exploration of their potential utility or derivative compounds in cancer treatment and prevention., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. This manuscript has not been previously published, and we have obtained unanimous agreement from all authors for its submission to European Journal of Pharmacology. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.We further confirm that any aspect of the work covered in this manuscript that has involved either experimental animals or human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study examines the impact of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) on various aspects of children's health-from the realms of growth and puberty to the nuanced characteristics of metabolic syndrome, diabetes, liver pathology, carcinogenic potential, and cardiovascular disorders. A comprehensive literature review was conducted using PubMed, with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method employing specific keywords related to child health, obesity, and insulin-like growth factors. This study reveals associations between insulin-like growth factor 1 and birth weight, early growth, and adiposity. Moreover, insulin-like growth factors play a pivotal role in regulating bone development and height during childhood, with potential implications for puberty onset. This research uncovers insulin-like growth factor 1 and insulin-like growth factor 2 as potential biomarkers and therapeutic targets for metabolic dysfunction-associated liver disease and hepatocellular carcinoma, and it also highlights the association between insulin-like growth factors (IGFs) and cancer. Additionally, this research explores the impact of insulin-like growth factors on cardiovascular health, noting their role in cardiomyocyte hypertrophy. Insulin-like growth factors play vital roles in human physiology, influencing growth and development from fetal stages to adulthood. The impact of maternal obesity on children's IGF levels is complex, influencing growth and carrying potential metabolic consequences. Imbalances in IGF levels are linked to a range of health conditions (e.g., insulin resistance, glucose intolerance, metabolic syndrome, and diabetes), prompting researchers to seek novel therapies and preventive strategies, offering challenges and opportunities in healthcare.

Objective: To establish a risk predictive model nomogram of acute kidney injury (AKI) in critically ill patients by combining urinary tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7), and to verify the predictive value of the model., Methods: A prospective observational study was conducted. The patients with acute respiratory failure or circulatory disorder admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from November 2017 to April 2020 were enrolled. The patients were enrolled within 24 hours of ICU admission, and their general conditions and relevant laboratory test indicators were collected. At the same time, urine was collected to determine the levels of biomarkers TIMP2 and IGFBP7, and TIMP2×IGFBP7 was calculated. Patients were divided into non-AKI and AKI groups according to whether grade 2 or 3 AKI occurred within 12 hours after enrollment. The general clinical data and urinary TIMP2×IGFBP7 levels of patients between the two groups were compared. The indicators with P < 0.1 in univariate analysis were included in the multivariate Logistic regression analysis to obtain the independent risk factors for grade 2 or 3 AKI within 12 hours in critical patients. An AKI risk predictive model nomogram was established, and the application value of the model was evaluated., Results: A total of 206 patients were finally enrolled, of whom 54 (26.2%) developed grade 2 or 3 AKI within 12 hours of enrollment, and 152 (73.8%) did not. Compared with the non-AKI group, the patients in the AKI group had higher body mass index (BMI), pre-enrollment serum creatinine (SCr), urinary TIMP2×IGFBP7 and proportion of using vasoactive drugs, and additional exposure to AKI (use of nephrotoxic drugs before enrollment) was more common. Multivariate Logistic regression analysis showed that BMI [odds ratio (OR) = 1.23, 95% confidence interval (95%CI) was 1.10-1.37, P = 0.000], pre-enrollment SCr (OR = 1.01, 95%CI was 1.00-1.02, P = 0.042), use of nephrotoxic drugs (OR = 2.84, 95%CI was 1.34-6.03, P = 0.007) and urinary TIMP2×IGFBP7 (OR = 2.19, 95%CI was 1.56-3.08, P = 0.000) was an independent risk factor for the occurrence of grade 2 or 3 AKI in critical patients. An AKI risk predictive model nomogram was constructed based on the independent risk factors of AKI. Bootstrap validation results showed that the model had good discrimination and calibration in internal validation. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of urinary TIMP2×IGFBP7 alone in predicting grade 2 or 3 AKI within 12 hours in critical patients was 0.74 (95%CI was 0.66-0.83), the optimal cut-off value was 1.40 (μg/L) 2 /1 000 (sensitivity was 66.7%, specificity was 85.0%), and the predictive performance of the model incorporating urinary TIMP2×IGFBP7 was significantly better than that of the model without urinary TIMP2×IGFBP7 [AUC (95%CI): 0.85 (0.79-0.91) vs. 0.77 (0.70-0.84), P = 0.005], net reclassification index (NRI) was 0.29 (95%CI was 0.08-0.50, P = 0.008), integrated discrimination improvement (IDI) was 0.13 (95%CI was 0.07-0.19, P < 0.001)., Conclusions: The AKI risk predictive model based on urinary TIMP2×IGFBP7 has high clinical value and is expected to be used to early predict the occurrence of AKI in critically ill patients.

As a new member of the insulin-like growth factors (Igfs), Igf3 was reported to play a vital role in fish reproduction. However, in spotted steed, the function of Igf3 remains largely unknown. In the present study, we identified and characterized Igf3 gene in spotted steed. Structural analysis showed that Igf3 contained five domains (B, C, A, D, E) and six conserved cysteine residues. The expression of Igf3 mRNA and protein were increased during ovary development and peaked in the maturation stage. The subcellular localization of IGF3 was highly expressed in granulosa cells and theca cells. Furthermore, recombinant IGF3 protein was produced and in vitro treatment with ovarian follicles significantly promoted the germinal vesicle breakdown (GVBD) rates of spotted steed follicles. The mRNA expression of cdc2 and cyclinB genes were significantly increased after IGF3 treatment, which were main components of maturation promoting factor (MPF). In addition, transcription levels of 3β-hsd, 20β-hsd, Cyp17a and Cyp19a1a were also changed. Taken together, these findings suggest that Igf3 is essential for ovary steroidogenesis and maturation in spotted steed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, gilthead sea bream ( Sparus aurata ) fast muscle myoblasts were stimulated with two pro-growth treatments, amino acids (AA) and insulin-like growth factor 1 (Igf-1), to analyze the transcriptional response of mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and to explore their possible regulatory network using bioinformatic approaches. AA had a higher impact on transcription (1795 mRNAs changed) compared to Igf-1 (385 mRNAs changed). Both treatments stimulated the transcription of mRNAs related to muscle differentiation (GO:0042692) and sarcomere (GO:0030017), while AA strongly stimulated DNA replication and cell division (GO:0007049). Both pro-growth treatments altered the transcription of over 100 miRNAs, including muscle-specific miRNAs (myomiRs), such as miR-133a/b , miR-206 , miR-499 , miR-1 , and miR-27a . Among 111 detected lncRNAs (>1 FPKM), only 30 were significantly changed by AA and 11 by Igf-1. Eight lncRNAs exhibited strong negative correlations with several mRNAs, suggesting a possible regulation, while 30 lncRNAs showed strong correlations and interactions with several miRNAs, suggesting a role as sponges. This work is the first step in the identification of the ncRNAs network controlling muscle development and growth in gilthead sea bream, pointing out potential regulatory mechanisms in response to pro-growth signals.

Acromegaly and gigantism are disorders caused by hypersecretion of growth hormone (GH), usually from pituitary adenomas. Although somatostatin analogues (SSA), dopamine agonists, and GH receptor antagonists are important therapeutic agents, all of these have issues with their effectiveness, safety, and/or convenience of use. To overcome these, we developed a GH-specific potent neutralizing a mouse monoclonal antibody (mAb) named 13H02. 13H02 selectively bound both to human and monkey GH with high affinity, and strongly inhibited the biological activity of GH in the Nb2 rat lymphoma cell proliferation assay. In hypophysectomized/GH-supplemented rats, a single subcutaneous administration of 13H02 significantly and dose-dependently lowered the serum insulin-like growth factor-1 levels. To pursue the therapeutic potential of this antibody for acromegaly and gigantism, we humanized 13H02 to reduce its immunogenicity and applied a single amino acid mutation in the Fc region to extend its serum half-life. The resulting antibody, Hu-13H02m, also showed GH-specific neutralizing activity, similar to the parental 13H02, and showed improved binding affinity to human FcRn., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Insulin-like growth factor I (IGF-I) has been suggested as an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD). In turn, nutrition has been associated with IGF-I levels and could be of importance in the pathogenesis of BPD. This study aimed to explore the association between nutrition, the IGF-I axis and the occurrence of BPD. Eighty-six preterm infants (44 male, mean gestational age: 29.0 weeks (standard deviation: 1.7 weeks)) were enrolled in an observational study. Serum IGF-I (µg/L) and insulin-like growth factor binding protein 3 (IGFBP-3; mg/L) were measured at birth and at 2, 4 and 6 weeks postnatal age. BPD was diagnosed at 36 weeks postmenstrual age. Twenty-nine infants were diagnosed with BPD. For every µg/L per week increase in IGF-I, the odds of BPD decreased (0.68, 95% CI 0.48-0.96, corrected for gestational age). The change in IGF-I in µg/L/week, gestational age in weeks and a week of predominant donor human milk feeding were associated with the occurrence of BPD in the multivariable analysis (respectively, OR 0.63 (0.43-0.92), OR 0.44 (0.26-0.76) and 7.6 (1.2-50.4)). IGFBP-3 was not associated with the occurrence of BPD in the multivariable analysis. In conclusion, a slow increase in IGF-I levels and a lower gestational age increase the odds of BPD. Donor human milk might increase the odds of BPD and should be further explored.

Serum levels of growth hormone (GH) and insulin-like growth factor (IGF)-I are crucial in the diagnosis and management of GH-related diseases. However, these levels are affected by nutritional and metabolic status. To elucidate the correlations between GH and IGF-I in various conditions, a retrospective analysis was performed for adult patients in which GH levels were examined by general practitioners during the period from January 2019 to December 2021. Of 642 patients, 33 patients were diagnosed with acromegaly, 21 were diagnosed with GH deficiency (GHD), and 588 were diagnosed with non-GH-related diseases (NGRD). In contrast to the positive correlations found between the levels of GH and IGF-I in patients with acromegaly ( R =0.50; P <0.001) and patients with GHD ( R =0.39; P =0.08), a negative correlation was found in the NGRD group ( R =-0.23; P <0.001). In that group, the results of multivariable analysis showed that GH levels were predominantly influenced by gender and body mass index (BMI), whereas IGF-I levels were modulated by albumin in addition to age and GH. Of note, in the NGRD group, there was an enhanced negative correlation between GH and IGF-I under conditions of BMI < 22 and albumin < 4.0 g/dL ( R =-0.45; P <0.001), and the negative correlation between GH and IGF-I was reinforced by excluding patients with other pituitary diseases and patients taking oral steroids ( R =-0.51; P <0.001 and R =-0.59; P <0.001, respectively). Collectively, the results indicate that attention should be given to the presence of a negative correlation between serum levels of GH and IGF-I, especially in lean and low-nutritious conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oguni, Yamamoto, Nakano, Soejima, Suyama, Takase, Yasuda, Hasegawa and Otsuka.)

Hybridization and polyploid breeding are the main approaches used to obtain new aquaculture varieties. Allotriploid crucian carp (3n) with rapid growth performance was generated by mating red crucian carp (RCC) with allotetraploids (4n). Fish growth is controlled by the growth hormone (GH)/insulin-like growth factor (IGF) axis. In the present study, we examined the expression characteristics of GH/IGF axis genes in hybrids F 1 , 4n, 3n, RCC and common carp (CC). The results showed that GHRa, GHRb, IGF1, IGF2, and IGF-1Ra were highly expressed in 3n compared with RCC and CC, whereas IGF3 was undetectable in the liver in RCC, CC and 3n. GHRa and GHRb had low expression in the 4n group. In hybrid F 1 , GHRa expression was low, whereas GHRb was highly expressed compared to the levels in RCC and CC. Moreover, in hybrid F 1 , the expression of IGF3 was higher, and the expression of IGF1 and IGF2 was lower than that in the RCC and CC, whereas the expression of IGF-1Ra was similar to that in RCC and CC. For the IGFBP genes, IGFBP1 had higher expression in 3n compared than that in RCC and CC, while other IGFBP genes were not high expressed in 3n. Among the genes detected in this study, 11 genes were nonadditively expressed in 3n, with 5 genes in the transgressive upregulation model. We proposed that the 11 nonadditive expression of GH/IGF axis genes is related to growth heterosis in 3n. This evidence provides new insights into hybridization and polyploid breeding from the perspective of hormone regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qing, Ren, Lou, Zhong, Zhou and Liu.)

Insulin-like growth factor 2 mRNA-binding proteins (IMPs, IGF2BPs) are RNA-binding proteins that regulate a variety of biological processes. In recent years, several studies have found that IGF2BPs play multiple roles in various biological processes, especially in cancer, and speculated on their mechanism of anticancer effect. In addition, targeting IGF2BPs or their downstream target gene has also received extensive attention as an effective treatment for different types of cancer. In this review, we summarized the recent progress on the role of IGF2BPs in cancers and their structural characteristics. We focused on describing the development of inhibitors targeting IGF2BPs and the prospects for further applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Herein, an antibody-protein-aptamer electrochemical biosensor was designed by highly efficient proximity-induced DNA hybridization on a tetrahedral DNA nanostructure (TDN) for ultrasensitive detection of human insulin-like growth factor-1 (IGF-1). Impressively, the IGF-1 antibody immobilized on the top vertex of the TDN could effectively capture the target protein with less steric effect, and the ferrocene-labeled signal probe (SP) bound on the bottom vertex of the TDN was close to the electrode surface for generating a strong initial signal. In the presence of target protein IGF-1 and an aptamer strand, an antibody-protein-aptamer sandwich could be formed on the top vertex of TDN, which would trigger proximity-induced DNA hybridization to release the SP on the bottom vertex of TDN; therefore, the signal response would decrease dramatically, enhancing the sensitivity of the biosensor. As a result, the linear range of the proposed biosensor for target IGF-1 was 1 fM to 1 nM with the limit of detection down to 0.47 fM, which was much lower than that of the traditional TDN designs on electrochemical biosensors. Surprisingly, the use of this approach offered an innovative approach for the sensitive detection of biomarkers and illness diagnosis.

Background and Objectives : Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBPs) are a family of secreted proteins involved in senescence and scarring, mainly synthetized in the liver. Here, we aimed to study the association of IGFBPs and their induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods : A total of 16-week-old male C57BL/6 mice weighing 23 ± 3 g were fed either methionine/choline-deficient (MCD) or control diet for 2, 8, or 12 weeks. Blood and liver samples were collected, and a histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in the liver and serum. Data were expressed as mean ± SD and analyzed by a one-way ANOVA followed by Tukey's test. Lineal regression models were applied for NAFLD and fibrosis progression. p < 0.05 was considered significant. Results : IGFBP-1 and -2 were increased in serum during NAFLD. IGFBP-7 was significantly increased in the serum in NASH compared with the controls. Senescence increased in NAFLD. Serum and liver IGFBP-7 as well as SA-β-gal activity increased as fibrosis progressed. Both IGFBP-7 and cellular senescence were significantly higher during NAFLD and fibrosis in MCD-fed mice. Conclusions : IGFBP-1, -2, and -7, through their consequent senescence, have a role in the progression of NAFLD and its associated fibrosis, being a plausible determinant in the progression from steatosis to NASH.

Background: The relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin resistance and type 2 diabetes mellitus (T2DM). In this retrospective observational study, we investigated relationships of IGF-1 with memory and executive function across people with normoglycemia, prediabetes, and T2DM., Methods: Data from the Midlife in the United States (MIDUS) study were used. Episodic memory and executive function were assessed using the Brief Test of Adult Cognition by Telephone approximately 21.42 ± 12.10 months prior to measuring IGF-1 levels from a fasting blood sample. Normoglycemia was identified as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) ≤5.6%. Prediabetes was identified as those without a physician diagnosis of diabetes and HbA1c between 5.7%-6.4%. T2DM was identified as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or anyone using an oral hypoglycemic medication. The associations were assessed using linear regressions controlling for age, sex, education, body mass index, C-reactive protein, HbA1c or homeostatic model of insulin resistance, MIDUS wave, exercise, smoking status, sleep quality, alcohol intake, oral hypoglycemic use, and insulin use., Results: The study included 1400 participants, which consisted of 583 normoglycemic (48.4% female, mean age 51.0 ± 12.2 years), 512 prediabetes (58.4% female, mean age 57.3 ± 11.8 years), and 305 T2DM participants (53.8% female, mean age 57.6 ± 11.5 years). Peripheral IGF-1 concentrations were lower (F 2,1397 = 28.29, p < 0.001) in people with prediabetes or T2DM, vs. normoglycemia. Participants with prediabetes or T2DM had lower episodic memory (F 2,1397 = 9.21, p < 0.001) and executive function (F 2,1397 = 20.29, p < 0.001) composite z-scores than people with normoglycemia. Higher IGF-1 concentrations were associated with better executive performance in individuals with prediabetes (β = 0.115 [0.028, 0.202], p = 0.010), but not in individuals with normoglycemia or T2DM. An interaction between IGF-1 and sex in predicting executive function was observed in the prediabetes group (β = -0.344, p = 0.042), where the relationship was weaker in females (β = 0.106 [-0.012, 0.224], p = 0.077) than males (β = 0.251 [0.123, 0.380], p < 0.001). No associations were seen between IGF-1 and memory., Conclusion: The results suggest that peripheral IGF-1 concentrations may be related to executive function, and that the relationship may be sex-specific and dependent on diabetes status., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Myocardial ischemia-reperfusion injury (MIRI) is a severe damage inflicted on the ischemic myocardium when blood flow is restored, and it commonly occurs in a wide range of cardiovascular diseases. Presently, no effective clinical treatment exists for MIRI. Accumulating evidence indicates that insulin-like growth factor-1 (IGF-1) plays a role in the intricate chain of cardiovascular events, in addition to its well-recognized growth-promoting and metabolic effects. IGF-1, a member of the insulin family, exhibits a broad spectrum of protective effects against ischemia/reperfusion injury in various tissues, especially the myocardium. In particular, earlier research has demonstrated that IGF-1 reduces cellular oxidative stress, improves mitochondrial function, interacts with noncoding RNAs, and activates cardiac downstream protective genes and protective signaling channels. This review aimed to summarize the role of IGF-1 in MIRI and elucidate its related mechanisms of action. In addition, IGF-1-related interventions for MIRI, such as ischemic preconditioning and post-conditioning, were discussed. The purpose of this review was to provide evidence supporting the activation of IGF-1 in MIRI and advocate its use as a therapeutic target., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Heterotopic ossification (HO) is the ectopic bone formation in soft tissues. Aside from hereditary HO, traumatic HO is common after orthopedic surgery, combat-related injuries, severe burns, or neurologic injuries. Recently, mammalian target of rapamycin (mTOR) was demonstrated to be involved in the chondrogenic and osteogenic processes of HO formation. However, its upstream signaling mechanism remains unknown. The current study used an Achilles tendon puncture-induced HO model to show that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. Micro-computed tomography imaging showed that IGF-1 not only accelerated the rate of osteogenesis and increased ectopic bone volume but also induced spontaneous ectopic bone formation in undamaged Achilles tendons. Blocking IGF-1 activity with IGF-1 antibody or IGF-1 receptor inhibitor picropodophyllin significantly inhibited HO formation. Mechanistically, IGF-1/IGF-1 receptor activates phosphatidylinositol 3-kinase (PI3K)/Akt signaling to promote the phosphorylation of mTOR, resulting in the chondrogenic and osteogenic differentiation of tendon-derived stem cells into chondrocytes and osteoblasts in vitro and in vivo. Inhibitors of PI3K (LY294002) and mTOR (rapamycin) both suppressed the IGF-1-stimulated mTOR signal and mitigated the formation of ectopic bones significantly. In conclusion, these results indicate that IGF-1 mediated the progression of traumatic HO through PI3K/Akt/mTOR signaling, and suppressing IGF-1 signaling cascades attenuated HO formation, providing a promising therapeutic strategy targeting HO., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication., Methods: Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16., Results: The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes., Conclusion: This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Despite the well-described optimal initial clinical response of sleeve gastrectomy (SG) in the treatment of obesity, some patients do not achieve optimal initial clinical response. Insulin-like growth factor-1 (IGF-1) has currently shown an association with post-bariatric surgery weight loss. This study aimed to assess the IGF-1 levels in female patients with obesity, the change after surgery, and their association with the metabolic profile and weight loss after surgery., Patients and Methods: This was a prospective study that was conducted on adult female patients who were recruited for SG. The patients underwent clinical and laboratory investigations that included the IGF-1 measurement. At the 1-year follow-up, the same clinical and laboratory measures were repeated., Results: This study included 100 female patients. At the 1-year follow-up, there was a statistically significant reduction in body mass index (BMI) (p < 0.001), fasting HbA1C levels (p < 0.001), and triglycerides (p < 0.001), as well as a statistically significant increase in HDL (p < 0.001) and IGF-1 (p < 0.001). Multiple regression analysis revealed that, among the patients baseline characteristics, the significant predictors for the percentage of total weight loss (%TWL) were the patients' BMI (p < 0.001) and IGF-1 levels (p < 0.001). The ROC curve showed that an IGF1 cutoff value of ≤ 23 ng/ml detected suboptimal initial clinical response, with a sensitivity of 95.35% and a specificity of 100%., Conclusion: This study underscores the significant impact of SG on weight loss and metabolic improvements in female patients. Baseline IGF-1 levels emerged as a crucial predictor of optimal initial clinical response., (© 2024. The Author(s).)

Recent years, invertebrate animals with clear genetic background and completed genome sequence have become very popular in biological research. Insulin and insulin-like peptides (ILPs) are a class of peptides having important physiological functions, including promotion of cell proliferation and differentiation, and body growth and development. To date, many invertebrates have been identified with multiple ILP families, whose structures and functions have become increasingly clear to scientists. This review summarizes the ILPs identified in the model Lepidopteran insect Bombyx mori, in the aspects of structures and classification, functions and pathways. A brief discussion on the ILPs from several other model insects, including Drosophila melanogaster, Aedes aegypti, and Apis mellifera, was also included. [ABSTRACT FROM AUTHOR]

• In mouse testes with Leydig cell tumor expression of GPER and PPAR is altered. • Treatment of MA-10 cells with BPA and its derivatives effects on GPER and PPAR expression. • There is a relation between expression of INSL3 and RLN and estrogen level in Leydig cell tumor. • PI3K-Akt-mTOR pathway and/or only mTOR is involved in GPER and PPAR interaction. The etiology and molecular characteristics of Leydig cell tumor (LCT) are scarcely known. From the research data stems that estrogen can be implicated in LCT induction and development, however it is not investigated in detail. Considering the above, herein we analyzed the relation between G-protein coupled membrane estrogen receptor, peroxisome proliferator-activated receptor and insulin-like family peptides (insulin-like 3 peptide; INSL3 and relaxin; RLN) expressions as well as estrogen level with impact of xenoestrogen (bisphenol A; BPA, tetrabromobisphenol A; TBBPA, and tetrachlorobisphenol A; TCBPA). While in our previous studies altered GPER-PPAR partnership was found in human LCT being a possible cause and/or additionally effecting on LCT development, here mouse testes with experimentally induced LCT and mouse tumor Leydig cell (MA-10) treated with BPA chemicals were examined. We revealed either diverse changes in expression or co-expression of GPER and PPAR in mouse LCT as well as in MA-10 cells after BPA analogues when compared to human LCT. Relationships between expression of INSL3, RLN, including co-expression, and estrogen level in human LCT, mouse LCT and MA-10 cells xenoestrogen-treated were found. Moreover, involvement of PI3K-Akt-mTOR pathway or only mTOR in the interactions of examined receptors and hormones was showed. Taken together, species, cell of origin, experimental system used and type of used chemical differences may result in diverse molecular characteristics of LCT. Estrogen/xenoestrogen may play a role in tumor Leydig cell proliferation and biochemical nature but this issue requires further studies. Experimentally-induced LCT in mouse testis and MA-10 cells after BPA exposure seem to be additional models for understanding some aspects of human LCT biology. [ABSTRACT FROM AUTHOR]

Abstract Tetrabromobisphenol A (TBBPA) is ubiquitous and its contents showing an increasing trend in the coastal environment. In order to investigate the effects of TBBPA on marine bivalves, juvenile manila clams Ruditapes phillipinarum were exposed to TBBPA for 28 days. The results showed that shell growth rate of juvenile clams after exposure to 62.5–1000 μg L−1 TBBPA for 28 d were significantly inhibited (p < 0.05). Then in order to link the changes in filtration rate, mRNA expression of insulin-like growth factor homologue (IGF) and tissue thyroid hormone (TH) contents to growth, juvenile clams were exposed to 62.5 and 500 μg L−1 TBBPA for 14 days. The transcriptional levels of neuroendocrine signals (NPF and insulin homologue) associated with filter feeding regulation, and genes of TH synthesis-related enzymes were also examined. The results showed that filtration rates was significantly reduced to 44.1% and 14% of controls after 14 d of exposure. In parallel, exposure to TBBPA significantly increased the expression levels of insulin which may elicit the filter feeding inhibition. TBBPA exposure caused alterations in tissue content of THs and mRNA expression of TH synthesis-related enzymes. However, the data showed increased T 3 content, T 3 /T 4 ratio and mRNA expression of IGF. These data demonstrated that the most important key event of TBBPA could be linked to growth impairment in juveniles was the reduction of filtration rate. These results provide a robust framework towards revealing the underlying mechanism of the growth inhibition caused by TBBPA on bivalves and understanding the adverse outcome pathway across taxonomic phyla. Highlights • Shell growth were significantly inhibited under 62.5–1000 μg L−1 TBBPA exposure. • Filtration rate decreased during 14 d exposure of 62.5 and 500 μg L−1 TBBPA. • Increased T 3 content with T 3 /T 4 ratio were observed after TBBPA exposure. • Exposure to TBBPA increased mRNA expression of IGF homologue and insulin homologue. [ABSTRACT FROM AUTHOR]

Abstract The peptide hormone relaxin mediates many biological actions including anti-fibrotic, vasodilatory, angiogenic, anti-inflammatory, anti-apoptotic, and organ protective effects across a range of tissues. At the cellular level, relaxin binds to the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1) to activate a variety of downstream signal transduction pathways. This signalling cascade is complex and also varies in diverse cellular backgrounds. Moreover, RXFP1 signalling shows crosstalk with other receptors to mediate some of its physiological functions. This review summarises known signalling pathways induced by acute versus chronic treatment with relaxin across a range of cell types, it describes RXFP1 crosstalk with other receptors, signalling pathways activated by other ligands targeting RXFP1, and it also outlines physiological relevance of RXFP1 signalling outputs. Comprehensive understanding of the mechanism of relaxin actions in fibrosis, vasodilation, as well as organ protection, will further support relaxin's clinical potential. Highlights • Signal transduction pathways activated by relaxin/RXFP1. • Crosstalk with other receptors and signalling pathways. • Signal transduction pathways activated by other ligands through RXFP1. [ABSTRACT FROM AUTHOR]

Insulin signaling is a conserved pathway in all metazoans. This pathway contributed toward primordial metazoans responding to a greater diversity of environmental signals by modulating nutritional storage, reproduction, and longevity. Most of our knowledge of insulin signaling in insects comes from the vinegar fly, Drosophila melanogaster , where it has been extensively studied and shown to control several physiological processes. Mosquitoes are the most important vectors of human disease in the world and their control constitutes a significant area of research. Recent studies have shown the importance of insulin signaling in multiple physiological processes such as reproduction, innate immunity, lifespan, and vectorial capacity in mosquitoes. Although insulin-like peptides have been identified and functionally characterized from many mosquito species, a comprehensive review of this pathway in mosquitoes is needed. To fill this gap, our review provides up-to-date knowledge of this subfield. [ABSTRACT FROM AUTHOR]

Mechanisms of glucose homeostasis are remarkably well conserved between the fruit fly Drosophila melanogaster and mammals. From the initial characterization of insulin signaling in the fly came the identification of downstream metabolic pathways for nutrient storage and utilization. Defects in these pathways lead to phenotypes that are analogous to diabetic states in mammals. These discoveries have stimulated interest in leveraging the fly to better understand the genetics of type 2 diabetes mellitus in humans. Type 2 diabetes results from insulin insufficiency in the context of ongoing insulin resistance. Although genetic susceptibility is thought to govern the propensity of individuals to develop type 2 diabetes mellitus under appropriate environmental conditions, many of the human genes associated with the disease in genome-wide association studies have not been functionally studied. Recent advances in the phenotyping of metabolic defects have positioned Drosophila as an excellent model for the functional characterization of large numbers of genes associated with type 2 diabetes mellitus. Here, we examine results from studies modeling metabolic disease in the fruit fly and compare findings to proposed mechanisms for diabetic phenotypes in mammals. We provide a systematic framework for assessing the contribution of gene candidates to insulin-secretion or insulin-resistance pathways relevant to diabetes pathogenesis.

Insulin-like growth factors (IGFs) are hormones that primarily stimulate and regulate animal physiological processes. In this study, we cloned and identified the open reading frame (ORF) cDNA sequences of IGF family genes: the insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), and insulin-like growth factor 3 (IGF3). We found that IGF1, IGF2, and IGF3 have a total length of 558, 648, and 585 base pairs (bp), which encoded a predicted protein with 185, 215, and 194 amino acids (aa), respectively. Multiple sequences and phylogenetic tree analysis showed that the mature golden pompano IGFs had been conserved and showed high similarities with other teleosts. The tissue distribution experiment showed that IGF1 and IGF2 mRNA levels were highly expressed in the liver of female and male fish. In contrast, IGF3 was highly expressed in the gonads and livers of male and female fish, suggesting a high influence on fish reproduction. The effect of fasting showed that IGF1 and mRNA expression had no significant difference in the liver but significantly decreased after long-term (7 days) fasting in the muscles and started to recover after refeeding. IGF2 mRNA expression showed no significant difference in the liver but had a significant difference in muscles for short-term (2 days) and long-term fasting, which started to recover after refeeding, suggesting muscles are more susceptible to both short-term and long-term fasting. In vitro incubation of 17β-estradiol (E 2 ) was observed to decrease the IGF1 and IGF3 mRNA expression level in a dose- (0.1, 1, and 10 μM) and time- (3, 6, and 12 h) dependent manner. In addition, E 2 had no effect on IGF2 mRNA expression levels in a time- and dose-dependent manner. The effect of 17α-methyltestosterone (MT) in vitro incubation was observed to significantly increase the IGF3 mRNA expression level in a time- and dose-dependent manner. MT had no effect on IGF2 mRNA but was observed to decrease the IGF1 mRNA expression in the liver. Taken together, these data indicate that E 2 and MT may either increase or decrease IGF expression in fish; this study provides basic knowledge and understanding of the expression and regulation of IGF family genes in relation to the nutritional status, somatic growth, and reproductive endocrinology of golden pompano for aquaculture development.

Background: Thyroid cancer (THCA) is the most common endocrine malignancy having a female predominance. The insulin-like growth factor (IGF) pathway contributed to the unregulated cell proliferation in multiple malignancies. We aimed to explore the IGF-related signature for THCA prognosis., Method: The TCGA-THCA dataset was collected from the Cancer Genome Atlas (TCGA) for screening of key prognostic genes. The limma R package was applied for differentially expressed genes (DEGs) and the clusterProfiler R package was used for the Gene Ontology (GO) and KEGG analysis of DEGs. Then, the un/multivariate and least absolute shrinkage and selection operator (Lasso) Cox regression analysis was used for the establishment of RiskScore model. Receiver Operating Characteristic (ROC) analysis was used to verify the model's predictive performance. CIBERSORT and MCP-counter algorithms were applied for immune infiltration analysis. Finally, we analyzed the mutation features and the correlation between the RiskScore and cancer hallmark pathway by using the GSEA., Result: We obtained 5 key RiskScore model genes for patient's risk stratification from the 721 DEGs. ROC analysis indicated that our model is an ideal classifier, the high-risk patients are associated with the poor prognosis, immune infiltration, high tumor mutation burden (TMB), stronger cancer stemness and stronger correlation with the typical cancer-activation pathways. A nomogram combined with multiple clinical features was developed and exhibited excellent performance upon long-term survival quantitative prediction., Conclusions: We constructed an excellent prognostic model RiskScore based on IGF-related signature and concluded that the IGF signal pathway may become a reliable prognostic phenotype in THCA intervention.

Piwi and its partner, Piwi-interacting RNA (piRNA), are pivotal in suppressing the harmful effects of transposable elements (TEs) linked to genomic insertional mutagenesis. While primarily active in Drosophila's adult gonadal tissues, causing sterility in its absence, Piwi's role in post-embryonic development remains unclear. Our study reveals Piwi's functional presence in the larval fat body, where it governs developmental growth through systemic insulin/insulin-like growth factor (IGF) signaling (IIS). Piwi knockdown in the fat body resulted in dysregulated TE expression, reduced developmental rate and body growth, and diminished systemic IIS activity. Notably, Piwi knockdown increased Imaginal Morphogenic Protein Late 2 (Imp-L2) expression, akin to insulin-like growth factor-binding protein 7 (IGFBP7), reducing systemic IIS and inhibiting body growth. This unveils a novel role for Piwi in larval adipose tissues, emphasizing its importance in regulating systemic IIS and overall organismal growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In vivo study was conducted to determine the role of insulin-like growth factors (IGF-II) related to dietary protein utilization. For this early juvenile stage of marine false clownfish Amphiprion ocellaris, 300 numbers of 20-day-old larvae (initial body weight of 18.2±0.027 mg/fish) were used as an experimental animal. Animals were fed for 12 weeks with different dietary protein levels (35, 40, 45, 50, and 55%), using Spirulina maxima as a major protein source. Proximate compositions and amino acid profile of the formulated diet were analyzed by the standard methods. Eventually, significant (P<0.05) mean, body weight gain, absolute growth rate, specific growth rate, and feed conversion ratio were obtained in the fishes fed with 50% of dietary protein, whereas, poor growth performance was noticed in 35% of the dietary protein level fed juveniles. The growth-responsible gene IGF-II expression studies showed the significant upregulation in the growth of the juveniles at 2.05±0.11 for 40%, 3.13±0.20 for 45%, 4.97±0.13 for 50%, and 4.33± 0.24 for 55%, which were higher than the control group 35%. The study concluded that 50% of dietary protein level is optimal for better growth indices in clownfish; A. ocellaris juveniles and IGF-II can be used as a potential marker gene to assess the growth indices in A. ocellaris., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Rationale: Experimental studies and epidemiological data in adults suggest that somatomedin-C (insulin-like growth factor-1, IGF-1) may play a role in asthma by modulating airway inflammation, bronchial hyperreactivity, and airway smooth muscle hyperplasia. However, its role in children with asthma is not well understood., Methods: We established a birth cohort with 339 Chilean pregnant mothers enrolled at the time of delivery from December 2014 to January 2016. We obtained cord blood at birth and followed the offspring every 6 months until 30 months of age, recording data on atopy, wheezing, and other respiratory illnesses. We measured IGF-1 in cord blood and determined the Asthma Predictive Index (API) at 30 months. The cohort was divided according to the API., Results: Complete data were available for 307/339 (91%) dyads, including 44 preschoolers with API+ and 263 with API-. Demographic characteristics were similar between groups, but mothers of API+ children had a higher prevalence of obesity, previous use of oral contraceptives, and higher education than those of API- children. API+ children had higher birth weight and significantly higher IGF-1 in cord blood (37.4 ± 13.2 in API+ vs. 30.5 ± 13.0 ng/ml in API-, p = .01). In the multivariable analysis, IGF-1 in cord blood remained independently associated with a higher risk of asthma (adjusted OR for API+ per ng/ml higher IGF-1 = 1.03 [1.0-1.06], p = .015)., Conclusions: Higher insulin-like growth factor-1 in cord blood is associated with asthma risk in the preschool years., (© 2023 Wiley Periodicals LLC.)

Introduction: Age-related blood-brain barrier (BBB) disruption, cerebromicrovascular senescence, and microvascular rarefaction substantially contribute to the pathogenesis of vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Previous studies established a causal link between age-related decline in circulating levels of insulin-like growth factor-1 (IGF-1), cerebromicrovascular dysfunction, and cognitive decline. The aim of our study was to determine the effect of IGF-1 signaling on senescence, BBB permeability, and vascular density in middle-age and old brains., Methods: Accelerated endothelial senescence was assessed in senescence reporter mice (VE-Cadherin-Cre ERT2 /Igf1r fl/fl × p16-3MR) using flow cytometry. To determine the functional consequences of impaired IGF-1 input to cerebromicrovascular endothelial cells, BBB integrity and capillary density were studied in mice with endothelium-specific knockout of IGF1R (VE-Cadherin-Cre ERT2 /Igf1r fl/fl ) using intravital two-photon microscopy., Results: In VE-Cadherin-Cre ERT2 /Igf1r fl/fl mice: (1) there was an increased presence of senescent endothelial cells; (2) cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3-40 kDa) is significantly increased, as compared to that of control mice, whereas decline in cortical capillary density does not reach statistical significance., Conclusions: These findings support the notion that IGF-1 signaling plays a crucial role in preserving a youthful cerebromicrovascular endothelial phenotype and maintaining the integrity of the BBB., (© 2023 John Wiley & Sons Ltd.)

The objective of this study was to investigate the mRNA expression of insulin-like growth factor-1 (IGF-1), pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α), serum immunoglobulin profiles (IgG and IgM), and lipid peroxidation status (MDA) in relation to pro-inflammatory cytokines. A case-controlled, prospective, and observational investigation was completed on 85 calves. Total RNA was isolated from whole blood samples of both the SIRS and healthy calves, followed by reverse transcription into cDNA. The resulting cDNAs were mixed with iTaq Universal SYBR Green Supermix and primers specific to the relevant genes using the Rotor-Gene Q instrument. After the reaction was completed, gene expressions were normalised against β-actin using the 2 -ΔΔCT method. The mRNA levels of pro-inflammatory cytokines namely (IL-1β [SIRS: 2.15 ± 0.55, Control: 1.13 ± 0.62; P = 0.001], IL-6 [SIRS: 2.82 ± 0.52, Control: 0.91 ± 0.11; P < 0.001], IL-18 [SIRS: 1.92 ± 0.41, Control: 0.99 ± 0.13; P < 0.001], and TNF-α [SIRS: 2.59 ± 0.28, Control: 0.93 ± 0.09; P < 0.001]) and IGF-1 (SIRS: 3.55 ± 0.55, Control: 0.91 ± 0.15; P < 0.001) were up-regulated in calves with SIRS, while serum IgG (SIRS: 4.16 ± 0.26, Control: 1.73 ± 0.17; P < 0.001), IgM (SIRS: 1.55 ± 0.11, Control: 1.09 ± 0.13; P < 0.001), and MDA levels (SIRS: 41.12 ± 3.48, Control: 3.76 ± 0.81; P < 0.001) increased significantly in these calves. Furthermore, significant (P < 0.01) positive correlations were found in calves with SIRS in relation to the expression levels of IL-1β, IL-6, IL-18, TNF-α, IGF-1, serum immunoglobulins, and MDA levels. These results suggest that IGF-1 could be a valuable pro-inflammatory marker, considering its high positive correlation with the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and markers (MDA, IgG, and IgM) in calves with SIRS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Insulin-like growth factor-1 (IGF-1) is involved in the pathology of non-alcoholic fatty liver disease (NAFLD) and ameliorates fatty infiltration in the liver. It is activated by growth hormone (GH); however, the role of GH-IGF-1 axis in NAFLD developmental phase has not been well identified. Therefore, in this study, we focused on the effect of IGF-1 in NAFLD pathology and GH excretion activation from the pituitary gland by peripheral autonomic neural pathways relaying liver-brain-gut pathway and by central neuropeptides., Methods: GH and IGF-1 levels were assessed in wild-type and melanocortin-4 receptor knockout mice upon the development of diet-induced NAFLD. The contribution of the peripheral autonomic nervous system connecting the liver-brain-gut axis was assessed by its blockade using capsaicin and that of the central nervous system was assessed by the expression of hypothalamic brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRH), which activates GH release from the pituitary gland., Results: In the NAFLD mouse models, the levels of GH and IGF-1 increased (p < .05). Further, hepatic fatty infiltration was suppressed even under peripheral autonomic nervous system blockade (p < .001), which inhibited gastric ghrelin expression. In mice with peripheral autonomic nervous blockade, hypothalamic BDNF and CRH were inhibited (p < .05), resulting in GH and IGF-1 excretion, whereas other neuropeptides of somatostatin and cortistatin showed no changes. These complementary effects were canceled in melanocortin-4 receptor knockout mice, which diminished BDNF and CRH release control., Conclusions: Our study demonstrates that the release of IGF-1 by the nervous system is a key factor in maintaining the pathological homeostasis of NAFLD, suggesting its therapeutic potential., (© 2023. Asian Pacific Association for the Study of the Liver.)

Objective: Preeclampsia (PE) is a pregnancy-specific condition featured by high blood pressure, edema, and proteinuria. Research about the role of microRNA (miR)-203 in PE remains insufficient. This experiment is designed to investigate the specific role of miR-203 in trophoblasts in PE., Study Design: miR-203 expression in placenta tissues of normal pregnant women and PE patients was examined to analyze the relevance between miR-203 and PE diagnostic efficiency and between miR-203 and blood pressure (systolic pressure and diastolic pressure) and proteinuria of PE patients. miR-203 expression was downregulated in hypoxia-cultured trophoblasts using miR-203 inhibitor to assess matrix metalloproteinase-9 (MMP-9) level. Then, the angiogenesis of trophoblasts with different treatments was determined. Subsequently, the target relation between miR-203 and insulin-like growth factor receptor 1 (IGF-1R) was predicted and verified. Additionally, the effect of IGF-1R in the mechanism of miR-203 modulating trophoblast vascular remodeling was detected., Results: miR-203 was overexpressed in the placenta of PE patients and it acted as a promising diagnostic indicator for PE. Moreover, miR-203 was positively associated with blood pressure (systolic pressure and diastolic pressure) and proteinuria of PE patients. miR-203 silencing in hypoxia-cultured trophoblasts enhanced trophoblast vascular remodeling. Mechanically, miR-203 bound to IGF-1R to suppress its transcription. IGF-1R downregulation counteracted the promotive effect of miR-203 silencing on trophoblast vascular remodeling., Conclusion: miR-203 was overexpressed in PE, and it targeted IGF-1R to limit trophoblast vascular remodeling., Key Points: · miR-203 is overexpressed in the placenta of PE patients.. · miR-203 acts as a potential diagnostic marker for PE.. · miR-203 targets IGF-1R to reduce trophoblast vascular remodeling in PE.., Competing Interests: None declared., (Thieme. All rights reserved.)