Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells.

Autor: Asrih M; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland., Dusaulcy R; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland., Gosmain Y; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland., Philippe J; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland., Somm E; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland., Jornayvaz FR; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland., Kang BE; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 16419, Suwon, Republic of Korea., Jo Y; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 16419, Suwon, Republic of Korea., Choi MJ; Research Center for Endocrine and Metabolic Diseases, Chungnam National University Hospital, Chungnam National University School of Medicine, 35015, Daejeon, Republic of Korea; Department of Medical Science, Chungnam National University School of Medicine, 35015, Daejeon, Republic of Korea., Yi HS; Research Center for Endocrine and Metabolic Diseases, Chungnam National University Hospital, Chungnam National University School of Medicine, 35015, Daejeon, Republic of Korea; Department of Medical Science, Chungnam National University School of Medicine, 35015, Daejeon, Republic of Korea., Ryu D; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 16419, Suwon, Republic of Korea; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, 16419, Suwon, Republic of Korea; Samsung Biomedical Research Institute, Samsung Medical Center, 06351, Seoul, Republic of Korea., Gariani K; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland. Electronic address: karim.gariani@hcuge.ch.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2022 Feb 05; Vol. 541, pp. 111503. Date of Electronic Publication: 2021 Nov 08.
DOI: 10.1016/j.mce.2021.111503
Abstrakt: Pancreatic beta cell dysfunction is a hallmark of type 2 diabetes. Growth differentiation factor 15 (GDF15), which is an energy homeostasis regulator, has been shown to improve several metabolic parameters in the context of diabetes. However, its effects on pancreatic beta-cell remain to be identified. We, therefore, performed experiments using cell models and histological sectioning of wild-type and knock-out GDF15 mice to determine the effect of GDF15 on insulin secretion and cell viability. A bioinformatics analysis was performed to identify GDF15-correlated genes. GDF15 prevents glucotoxicity-mediated altered glucose-stimulated insulin secretion (GSIS) and connexin-36 downregulation. Inhibition of endogenous GDF15 reduced GSIS in cultured mouse beta-cells under standard conditions while it had no impact on GSIS in cells exposed to glucolipotoxicity, which is a diabetogenic condition. Furthermore, this inhibition exacerbated glucolipotoxicity-reduced cell survival. This suggests that endogenous GDF15 in beta-cell is required for cell survival but not GSIS in the context of glucolipotoxicity.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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