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Background: Pancreatic neuroendocrine neoplasms (pNENs) are rare primary tumors of the pancreas. Although these tumors are heterogeneous and can be classified as functional or non-functional according to pancreatic endocrine biomarkers, the more prevalent type is non-functional pNENs with endocrine differentiation but with non-specific symptoms and often late diagnoses. The treatment option for patients often involves surgical management, but the reported outcomes, especially on insulin secretion change and the trend of diabetes in these patients, varied to date. Hence, the purpose of this clinical report is to study the functional change of pancreatic β- cell corresponding to the mass of tumorectomy of pNEN in a diabetic patient. Case Presentation: We reported that a 39-year-old man with diabetes was found complicated with neuroendocrine neoplasm. He was admitted to the General Surgery of our hospital for further examination and therapy. The patient received a pancreatectomy + splenectomy + lymphadenectomy on the pancreatic body and tail. We analyzed the pancreatic mass change and performed Oral Glucose Tolerance Test (OGTT) before and after the surgery to evaluate the function of the pancreas. Conclusions: This case may provide us a reference to predict the extent of islet function loss before the pancreatectomy, and apply personalized hypoglycemic therapy after surgery in these patients.

Solid particles mixed in the oil cause erosion of hydraulic spool valves, and these valves may fail in severe erosion. In this article, with the help of the Euler–Lagrange solver, a numerical model...

GLP-1 receptor agonists (GLP-1RAs) and SGLT-2 inhibitors (SGLT-2is) are novel antidiabetic medications associated with considerable cardiovascular benefits therapying treatment of diabetic patients. GLP-1 exhibits atherosclerosis resistance, whereas SGLT-2i acts to ameliorate the neuroendocrine state in the patients with chronic heart failure. Despite their distinct modes of action, both factors share pathways by regulating the central nervous system (CNS). While numerous preclinical and clinical studies have demonstrated that GLP-1 can access various nuclei associated with energy homeostasis and hedonic eating in the CNS via blood–brain barrier (BBB), research on the activity of SGLT-2is remains limited. In our previous studies, we demonstrated that both GLP-1 receptor agonists (GLP-1RAs) liraglutide and exenatide, as well as an SGLT-2i, dapagliflozin, could activate various nuclei and pathways in the CNS of Sprague Dawley (SD) rats and C57BL/6 mice, respectively. Moreover, our results revealed similarities and differences in neural pathways, which possibly regulated different metabolic effects of GLP-1RA and SGLT-2i via sympathetic and parasympathetic systems in the CNS, such as feeding, blood glucose regulation and cardiovascular activities (arterial blood pressure and heart rate control). In the present article, we extensively discuss recent preclinical studies on the effects of GLP-1RAs and SGLT-2is on the CNS actions, with the aim of providing a theoretical explanation on their mechanism of action in improvement of the macro-cardiovascular risk and reducing incidence of diabetic complications. Overall, these findings are expected to guide future drug design approaches.

Purpose: Our primary objective in this study is to determine the relationship between serum iron (Fe3+) and thyroid functions in type 2 diabetes mellitus (T2DM) patients. Materials and Methods: Glucose metabolic parameters, trace elements, such as Fe3+, and thyroid functions for 1657 type 2 diabetic patients treated at the Shanghai Pudong Hospital's Department of Endocrinology from 2018 to 2021 were assessed. Results: Variations in free thyroid hormones (FTH) and total thyroid hormones (TTH) were insignificant; however, thyroid-stimulating hormone (TSH) levels were markedly elevated in patients with positive thyroid peroxidase antibody (TPOAb) and/or positive antithyroglobulin antibody (TgAb) (p0.05). The multilinear regression model showed that TT3 (β=0.702), eGFR (β=0.109), Fe3+ (β=0.003), female gender (β=-0.061), and age (β=-0.061) were the major determinants for FT3 change. Moreover, renal function, which was represented as the estimated glomerular filtration rate (eGFR), had no effects on Fe3+ and TSH levels but on the levels of FTH and TTH (p0.05). Conclusions: In addition to age, gender, and renal functions, serum Fe3+ levels in T2DM patients have a significant relationship with thyroid functions.

Purpose This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. Material and methods Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence. Results Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. Conclusion This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.

Congying Liu,1 Junhong Pan,1 Song Wen,1 Thiquynhnga Nguyen,1 Dongxiang Xu,1 Chaoxun Wang,1 Xinlu Yuan,1 Zhongqiu Wen,2 Ligang Zhou1,3 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Department of Information Center, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 3Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of ChinaCorrespondence: Ligang ZhouDepartment of Endocrinology, Shanghai Pudong Hospital, Fudan University, 2800 Gongwei Road, Huinan Town, Pudong New Area, Shanghai, 201399, People’s Republic of ChinaTel +8613611927616Email zhouligang@yahoo.comObjective: We aimed to evaluate the relationship between thyroid-stimulating hormone (TSH) and bone mineral density (BMD) in euthyroid type 2 diabetes (T2D).Methods: This retrospective analysis enrolled 439 T2D patients with normal thyroid function, including 226 males and 213 females. All the female patients were postmenopausal. Serum glycosylated hemoglobin A1c (HbA1c), TSH, free triiodothyronine (FT3), and free thyroxine (FT4) concentrations were analyzed. BMD of the lumbar spine (L1–L4), femoral neck, and hip joint was determined using dual-energy X-ray absorptiometry.Results: The patients were grouped based on tri-sectional quantiles of the TSH levels: 0.55∼ 1.70mIU/L (Group 1), 1.71∼ 2.58mIU/L (Group 2), and 2.59∼ 4.74mIU/L (Group 3). Our data showed that, in male patients, no difference in BMD was identified among groups. In postmenopausal women, unlike at the lumbar spine (P = 0.459), the mean BMD at the femoral neck (P = 0.014) and hip joint (P = 0.014) had a statistical difference among groups and increased with TSH level. In addition, our analysis demonstrated that TSH levels shown no correlation with BMD at all sites in males. However, in females, BMD at the femoral neck (r = 0.156, P = 0.023) and hip joint (r = 0.172, P = 0.012) had a positive correlation with TSH levels. After adjusting for age and BMI, multiple regression analysis showed that TSH levels influenced BMD at the femoral neck (β = 0.188, P = 0.001) and hip joint (β = 0.204, P = 0.001) in female patients.Conclusion: In summary, our data demonstrates that low TSH levels are associated with decreased BMD at the femoral neck and hip joint in postmenopausal T2D women with euthyroidism.Keywords: type 2 diabetes, thyroid-stimulating hormone, bone mineral density, menopause

The purpose of the present study was to explore the effects of emodin on renal injury in a BXSB mouse model of lupus and its mechanisms. BXSB mice were fed different concentrations of emodin (0, 5, 10 and 20 mg/kg.d), and the levels of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) and fibronectin (FN) levels in the glomeruli and serum levels of the anti-dsDNA antibody were determined. Mesangial cells (MCs) were cultured in vitro, and IgG-type anti-dsDNA antibody and/or emodin were added to the MC culture supernatant. In addition, TNF-α small interfering RNA (siRNA) was transfected into MCs to explore the mechanism of action of emodin. The results showed that the mice fed emodin presented decreases in the urinary protein content and glomerular TNF-α, ICAM-1 and FN levels (P

Metformin, the first-line drug to treat type 2 diabetes, inhibits mitochondrial glycerolphosphate dehydrogenase in the liver to suppress gluconeogenesis. The major adverse effects caused by metformin were lactic acidosis and gastrointestinal discomfort. Therefore, there is need to develop a strategy with excellent permeability and appropriate retention effects.In this study, we synthesized a simple and biocompatible PolyMetformin (denoted as PolyMet) through conjugation of PEI1.8K with dicyandiamide, and then formed PolyMet-hyaluronic acid (HA) nanocomplexs by electrostatic self-assembly of the polycationic PolyMet and polyanionic hyaluronic acid (HA). Similar to metformin, the PolyMet-HA nanocomplexs could reduce the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro. In SHIP2-overexpressing myotubes, PolyMet-HA nanocomplexes ameliorated glucose uptake by downregulating glucose transporter 4 endocytosis. PolyMet-HA nanocomplexes also could restore Akt signaling and protect the podocyte from apoptosis induced by SHIP2 overexpression. In essence, the PolyMet-HA nanocomplexes act similarly to metformin and increase glucose uptake, and maybe have a potential role in the treatment of type 2 diabetes.

Incretin-based therapy is now a prevalent treatment option for patients with type 2 diabetes mellitus (T2DM). It has been associated with considerably good results in the management of hyperglycemia with cardiac or nephron-benefits. For this reason, it is recommended for individuals with cardiovascular diseases in many clinical guidelines. As an incretin hormone, glucagon-like peptide-1 (GLP-1) possesses multiple metabolic benefits such as optimizing energy usage, maintaining body weight, β cell preservation, and suppressing neurodegeneration. However, recent studies indicate that oral antidiabetic medications interact with endogenous or exogenous GLP-1. Since these drugs are transported to distal intestine portions, there are concerns whether these oral drugs directly stimulate intestinal L cells which release GLP-1, or whether they do so via indirect inhibition of the activity of dipeptidyl peptidase-IV (DPP-IV). In this review, we discuss the metabolic relationships between oral antihyperglycemic drugs from the aspect of gut, microbiota, hormones, β cell function, central nervous system, and other cellular mechanisms.

Additional file 3: Table S2. Primers sequences of randomly selected eight circRNAs and two genes for another reverse transcription-quantitative polymerase chain-reaction (RT-qPCR).

Additional file 1: Table S1. The fold-change and p value of 93 differentially expressed circRNAs.

Supplemental material, sj-pdf-1-jba-10.1177_0885328220947343 for PolyMet-HA nanocomplexs regulates glucose uptake by inhibiting SHIP2 activity by Xinlu Yuan, Ling Ding, Jianjun Diao, Song Wen, Chenglin Xu, Ligang Zhou and Anqing Du in Journal of Biomaterials Applications

Additional file 4: Table S3. The circRNAs-miRNAs interaction network of top 300 dysregulated circRNAs.

A new sorbent was synthesized for restricted-access matrix solid phase extraction (RAM-SPE) of the diabetes drugs metformin (MET) and glimepiride (Glim). Mesoporous silica layers were placed on Fe3O4-magnetized graphene modified with sulfo-functionalized pore walls (denoted as magG@mSiO2-SO3H composites). The composites have a large specific surface (173 m2·g−1), appropriate pore sizes (typically 3.7 nm), and sulfo-functionalized pore walls. Magnetic separation can be accomplished within 10 s. The unique properties of the composites allow both MET and Glim to be selectively and quickly extracted from plasma sample. Following magnetic separation and elution by 50% aqueous acetonitrile with 4% ammonium solution, the two drugs were quantified by LC-MS/MS analysis. The assay has high selectivity, good linearity (2.5–4000 ng•mL−1 for MET and 0.02–1600 ng•mL−1 for Glim), a low detection limit (as low as 60 pg•mL−1 for MET and 1 pg•mL−1 for Glim), excellent recovery (above 92.2%), and good precision (RSDs

Type 2 diabetes mellitus (T2DM) is a chronic disease affected with complex risk factors and has been regarded as one of the major social burdens due to its high occurrence. In this study, we aim to incorporate the idea of evidence based medicine (EBM) into our diabetes risk factor App development. We acquired and extracted the relative risk of different risk factors from relevant literature by searching academic databases. A total of 19 items of risk factors in our daily lives has been finally selected. To design App graphic interface, a total of three pages were designed to let user answer the questions and show the results of their level or risk to have T2DM. We validated the feasibility of our App in 100 users and the results were promising. Therefore, the personalized EBM diabetes risk factor calculator might be a feasible approach to remind those T2DM risky populations by revealing their potential risk factors, thus making implementation of personalized and prevention medicine achievable at hand.

Serum fatty acid-binding protein 4 (FABP4) has been linked to renal dysfunction. This study evaluated the association between serum FABP4 and the radioisotope glomerular filtration rate (rGFR) in type 2 diabetic patients (T2DM) with early diabetic nephropathy. Twenty healthy controls and 172 patients with T2DM were enrolled. Serum FABP4 and renal impairment biomarkers including urinary albumin-to-creatinine ratio (UACR), serum retinal-binding protein 4 (RBP4), urinary cystatin C-to-creatinine ratio (CysC/Cr), and neutrophil gelatinase-associated lipocalin-to-creatinine ratio (NGAL/Cr) were measured. Diethylenetriaminepentaacetic acid (99mTc-DTPA) was used to test rGFR. Serum FABP4 levels were higher in T2DM patients compared with the controls. There was no significant correlation between serum FABP4 and UACR in patients with T2DM. Multivariate stepwise regression analysis showed that, in patients with T2DM, FABP4 was significantly associated with rGFR while CysC/Cr and RBP4 were significantly associated with UACR independently. But UACR had no independent association with rGFR. NGAL/Cr had no significant correlation with either rGFR or UACR. FABP4 might be an early biomarker for diabetic nephropathy if combined with UACR.

Aims/Introduction Previous studies have shown that glucose peak time during the oral glucose tolerance test varies in type 2 diabetes patients; however, characteristics of this heterogeneity remain unclear. This research aimed to investigate the characteristics of delayed glucose peak time in type 2 diabetes. Materials and Methods A total of 178 participants who underwent the oral glucose tolerance test were divided into five groups according to glucose peak time. Results A total of 25 participants with normal glucose tolerance had a glucose peak at 30 min. Among participants with type 2 diabetes, 28 had a glucose peak at 60 min, 48 at 90 min, 45 at 120 min and 32 at 150 min. With the glucose peak time delayed, glycated hemoglobin, area under the glucose curve and homeostatic model assessment of insulin resistance increased gradually (P = 0.038, P < 0.0001, P < 0.0001, respectively), and oral glucose insulin sensitivity, homeostatic model assessment of β‐cell function, insulinogenic index, modified β‐cell function index and disposition indices decreased (P < 0.0001 for all). On multinominal logistic regression, insulinogenic index (odds ratio 0.73, 95% confidence interval 0.57–0.93, P = 0.01), modified β‐cell function index (odds ratio 0.67, 95% confidence interval 0.47–0.94, P = 0.023) and oral glucose insulin sensitivity (odds ratio 0.91, 95% confidence interval 0.87–0.96, P < 0.0001) were independently correlated with delayed glucose peak time. Conclusions Delay in glucose peak time indicated an increase in blood glucose and a decrease in insulin sensitivity and secretion. Furthermore, insulinogenic index, modified β‐cell function index and oral glucose insulin sensitivity contributed to delayed glucose peak time.

Oxidative stress is thought to be critical for the pathogenesis of hepatic steatosis and its progress to non-alcoholic steatohepatitis. Berberine (BBR) can improve hepatic steatosis. In this study, we investigated the role of BBR in ameliorating oxidative stress. Lipid accumulation was measured in the livers of C57BL/6 mice fed a high fat diet (HFD) or a normal diet for 8 weeks, then either received BBR or vehicle for the study duration. Nrf2 distribution was detected in male Sprague-Dawley rats’ livers in vivo and in Huh7 cells in vitro. ROS generation and mitochondrial complex expression was measured in Huh7 cells. HepG2 cells were employed for the measurement of oxygen consumption rates. Our results showed that BBR reduced triglyceride accumulation in the liver of HFD-fed mice. The activation and nuclear distribution of Nrf2 was decreased in the hepatocytes of rats that received BBR treatment, while on a HFD. BBR also markedly reduced Nox2-dependent cytoplasmic ROS production and mitochondrial ROS production, which was mediated by the down-regulation of Complex I and III expression. In conclusion, BBR has a great potential to reduce the effects of oxidative stress, which likely contributes to its protective effect in inhibiting the progression of hepatic steatosis to steatohepatitis.

Tissue-engineered nerve grafts (TENGs), typically consisting of a neural scaffold included with support cells and/or growth factors, represent a promising alternative to autologous nerve grafts for surgical repair of large peripheral nerve gaps. Here, we developed a new design of TENGs by introducing bone marrow mesenchymal stem cells (MSCs) of rats, as support cells, into a silk fibroin (SF)-based scaffold, which was composed of an SF nerve guidance conduit and oriented SF filaments as the conduit lumen filler. The biomaterial SF had been tested to possess good biocompatibility and noncytoxicity with MSCs before the TENG was implanted to bridge a 10-mm-long gap in rat sciatic nerve. Functional and histological assessments showed that at 12 weeks after nerve grafting, TENGs yielded an improved outcome of nerve regeneration and functional recovery, which was better than that achieved by SF scaffolds and close to that by autologous nerve grafts. During 1-4 weeks after nerve grafting, MSCs contained in the TENG significantly accelerated axonal growth, displaying a positive reaction to S-100 (a Schwann cell marker). During 1-3 weeks after nerve grafting, MSCs contained in the TENG led to gene expression upregulation of S100 and several growth factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor). These results suggest that the cell behaviors and neurotrophic functions of MSCs might be responsible for their promoting effects on peripheral nerve regeneration.

Studies have identified that type 2 diabetes mellitus (T2DM) patients displayed higher levels of plasma peroxiredoxin1(PRDX1) than non-diabetics. However, the impact of PRDX1 on insulin resistance and the underlying mechanism remains totally unknown. Here, we investigated the influence of PRDX1 on hepatic insulin resistance. We showed that the protein and mRNA levels of PRDX1 were significantly elevated under insulin-resistant conditions. In addition, we showed that interference of PRDX1 ameliorated palmitate-induced insulin resistance in HepG2 cells, which was indicated by elevated phosphorylation of protein kinase B (AKT) and of glycogen synthase kinase-3 (GSK3β). Furthermore, the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), two key gluconeogenic enzymes, were down-regulated following PRDX1 depletion. Accordingly, glucose uptake was suppressed in PRDX1-interferred HepG2 cells. In addition, Over-expression of PRDX1 enhanced PA-induced insulin resistance in HepG2 cells. Moreover, we found that knocking down PRDX1 improves insulin sensitivity and decreased the activation of p38 mitogen-activated protein kinase (p38MAPK). Our results demonstrate that PRDX1 can induce hepatic insulin resistance by activating p38MAPK signaling and identifies potential targets for new treatments.

Background Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder that currently lacks effective treatment. Berberine (BBR), a botanic compound isolated from traditional Chinese medicine, exhibits a potent therapeutic potential for the metabolic disease. The current study aimed to understand the mechanisms underlying the therapeutic effect of BBR in NAFLD. Methods We performed systematical analyses on hepatic expression profiles of mRNAs and long noncoding RNAs (lncRNAs) in a high-fat diet (HFD)-induced steatotic animal model with or without BBR treatment. The study was conducted by using the methods of bioinformatics, including hierarchical clustering, gene enrichment and gene co-expression networks analysis. The effect of BBR on the expression profile of some interesting genes was confirmed by quantitative RT-PCR and further studied in a human hepatic cell line, Huh7. Results We found that a large group of genes including 881 mRNAs and 538 lncRNAs whose expression in the steatotic liver was reversed by BBR treatment, suggesting a global effect of BBR in modulating hepatic gene expression profiles. Among the BBR-regulated genes, we identified several modules and numerous significant genes that were associated with liver metabolism and NAFLD-related functions. Specifically, a conserved lncRNA, MRAK052686, was found strongly correlated with the antioxidant factor Nrf2, and both genes were down-regulated by the steatotic liver. Moreover, the reduced expression of MRAK052686 and Nrf2 was completely reversed by BBR treatment, suggesting a new mechanism accounting for the therapeutic effect of BBR. Conclusions The findings for the first time provide a new genetic insight into the pharmaceutical mechanism of BBR in protecting against NAFLD. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0383-6) contains supplementary material, which is available to authorized users.