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Start Over Topic insulin resistance Publication Year Range Last 10 years
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1. Piperine modulates IR/Akt/GLUT4 pathways to mitigate insulin resistance: Evidence from animal and computational studies.

Author

Prasad M, Jayaraman S, Natarajan SR, Veeraraghavan VP, Krishnamoorthy R, Gatasheh MK, Palanisamy CP, and Elrobh M

Subjects
Humans, Rats, Animals, Proto-Oncogene Proteins c-akt metabolism, Molecular Docking Simulation, Antioxidants pharmacology, Quality of Life, Insulin metabolism, Diet, High-Fat adverse effects, Insulin Resistance, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental metabolism
Abstract

The global prevalence of diabetes mellitus is rising, especially in India. Medicinal herbs, whether used alone or in combination with conventional medicines, have shown promise in managing diabetes and improving overall well-being. Piperine (PIP), a major bioactive compound found in pepper, is gaining attention for its beneficial properties. This study aimed to assess whether PIP could alleviate diabetes by targeting insulin pathway-related molecules in the adipose tissue of rats on a high-fat diet (HFD). After 60 days on the HFD, rats received PIP at a dose of 40 mg/kg body weight for one month. The results showed that PIP significantly improved metabolic indicators, antioxidant enzymes, and carbohydrate metabolic enzymes. It also regulated the mRNA and protein expression of insulin signaling, which had been disrupted by the diet and sucrose intake. Molecular docking analysis also revealed strong binding of PIP to key diabetes-related regulatory proteins, including Akt (-6.2 kcal/mol), IR (-7.02 kcal/mol), IRS-1 (-6.86 kcal/mol), GLUT4 (-6.24 kcal/mol), AS160 (-6.28 kcal/mol), and β-arrestin (-6.01 kcal/mol). Hence, PIP may influence the regulation of glucose metabolism through effective interactions with these proteins, thereby controlling blood sugar levels due to its potent antilipidemic and antioxidant properties. In conclusion, our study provides in vivo experimental evidence against the HFD-induced T2DM model for the first time, making PIP a potential natural remedy to enhance the quality of life for diabetic patients and aid in their management., 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.)

Published
2023
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2. Transplantation of neuregulin 4-overexpressing adipose-derived mesenchymal stem cells ameliorates insulin resistance by attenuating hepatic steatosis.

Author

Wang W, Zhang Y, Yang C, Wang Y, Shen J, Shi M, and Wang B

Subjects
Adipose Tissue cytology, Adipose Tissue metabolism, Animals, Cells, Cultured, Cholesterol metabolism, Glucose Transporter Type 4 metabolism, Lipogenesis, Liver metabolism, Male, Mesenchymal Stem Cells cytology, Mice, Mice, Inbred C57BL, Neuregulins metabolism, Sterol Regulatory Element Binding Protein 1 metabolism, Triglycerides metabolism, Tumor Necrosis Factor-alpha metabolism, Fatty Liver therapy, Genetic Therapy methods, Insulin Resistance, Mesenchymal Stem Cell Transplantation methods, Mesenchymal Stem Cells metabolism, Neuregulins genetics
Abstract

Impact Statement: Due to high-fat and high-sugar diets accompanied by sedentary lifestyles, diabetes has become a global epidemic. Literature findings suggest a potential therapeutic effect of Nrg4 on treating obesity-related metabolic disorders including type 2 diabetes (T2D). Adipose tissue-derived MSCs (ADSCs) were used in our study as they are abundant and can be harvested with minimally invasive procedures. In the end, our study reveals that ADSC transplantation improves glucose tolerance and metabolic balance in HFD-fed mice by multiple mechanisms, including upregulating GLUT4 expression and suppressing inflammation. More importantly, our study shows that Nrg4 overexpression could improve the efficacy of ADSCs in ameliorating insulin resistance (IR) and other obesity-related metabolic disorders, given the function of Nrg4 in attenuating hepatic lipogenesis. It would provide a new therapeutic strategy for the treatment of obesity, IR, and T2D.

Published
2019
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3. Mid-childhood fat mass and airflow limitation at 15 years:The mediating role of insulin resistance and C-reactive protein

Author

Gabriela P. Peralta, Raquel Granell, Annabelle Bédard, Anne‐Elie Carsin, Elaine Fuertes, Laura D. Howe, Sandra Márquez, Deborah L. Jarvis, Judith Garcia‐Aymerich, CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Universität Zürich [Zürich] = University of Zurich (UZH), University of Bristol [Bristol], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hospital del Mar Medical Research Institute [Barcelona, Spain] (IMIM), Imperial College London, Wellcome Trust, WT, Medical Research Council, MRC: 076467/Z/05/Z, G0401540/73080, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, MICINN, Horizon 2020: 633212, The present analyses are part of the Aging Lungs in European Cohorts (ALEC) Study ( www.alecstudy.org ), which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 633212. The content of this article reflects only the authors' views, and the European Commission is not liable for any use that may be made of the information contained therein. The UK Medical Research Council and Wellcome (Grant reference: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Laura Howe and Raquel Granell will serve as guarantors for the contents of this paper. A comprehensive list of grant funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). Specifically, grants from Wellcome Trust and MRC (076467/Z/05/Z and G0401540/73080) supported the collection of body composition and lung function data at 15 years. We acknowledge support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018‐000806‐S), and support from the Generalitat de Catalunya through the CERCA Program., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), HAL UVSQ, Équipe, and Aging Lungs in European Cohorts - ALEC - - H20202015-05-01 - 2019-04-30 - 633212 - VALID

Subjects
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, obesity, Immunology, ALSPAC, C-reactive protein, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, insulin resistance, Pediatrics, Perinatology and Child Health, Immunology and Allergy, epidemiology, mediation, airflow limitation
Abstract

Key MessageAlthough obesity measures have been consistently associated with a lower FEV1/FVC ratio in adolescents, no previous study has assessed the underlying mechanisms of this association This population-based study assessed whether insulin resistance and CRP levels at 15 years partially mediate the association between fat mass and FEV1/FVC using a causal mediation analysis approach. The findings suggest that insulin resistance at 15 years may mediate over 20% of this association, but no evidence of a mediating role of CRP was found. Further, longitudinal studies that evaluate other biomarkers of systemic inflammation and examine other potential mechanisms are needed to better understand the pathways linking obesity and respiratory health in adolescence. This is key for public health interventions and targeting clinical interventions.AbstractBackgroundWe previously reported an association of high fat mass levels from age 9 to 15 years with lower forced expiratory flow in 1 s (FEV1)/forced vital capacity (FVC) ratio (i.e., increased risk of airflow limitation) at 15 years. Here, we aimed to assess whether insulin resistance and C-reactive protein (CRP) at 15 years partially mediate this association.MethodsWe included 2263 children from the UK Avon Longitudinal Study of Parents and Children population-based cohort (ALSPAC). Four fat mass index (FMI) trajectories (“low,” “medium-low,” “medium-high,” “high”) from 9 to 15 years were previously identified using Group-Based Trajectory Modeling. Data on CRP, glucose, insulin, and post-bronchodilator FEV1/FVC were available at 15 years. We defined insulin resistance by the homeostasis model assessment-estimated insulin resistance index (HOMA-IR). We used adjusted linear regression models and a causal mediation analysis to assess the mediating role of HOMA-IR and CRP.ResultsCompared to children in the “low” FMI trajectory, children in the “medium-high” and “high” FMI trajectories had lower FEV1/FVC at 15 years. The percentage of the total effect explained by HOMA-IR was 19.8% [−114.1 to 170.0] and 20.4% [1.6 to 69.0] for the “medium-high” and “high” trajectories, respectively. In contrast, there was little evidence for a mediating role of CRP.ConclusionThe association between mid-childhood fat mass and FEV1/FVC ratio at 15 years may be partially mediated by insulin resistance.

Published
2022