Role of pancreatic transcription factors in maintenance of mature β-cell function

International Journal of Molecular Sciences
Hideaki Kaneto, Taka-aki Matsuoka

Abstract

A variety of pancreatic transcription factors including PDX-1 and MafA play crucial roles in the pancreas and function for the maintenance of mature β-cell function. However, when β-cells are chronically exposed to hyperglycemia, expression and/or activities of such transcription factors are reduced, which leads to deterioration of b-cell function. These phenomena are well known as β-cell glucose toxicity in practical medicine as well as in the islet biology research area. Here we describe the possible mechanism for β-cell glucose toxicity found in type 2 diabetes. It is likely that reduced expression levels of PDX-1 and MafA lead to suppression of insulin biosynthesis and secretion. In addition, expression levels of incretin receptors (GLP-1 and GIP receptors) in β-cells are decreased, which likely contributes to the impaired incretin effects found in diabetes. Taken together, down-regulation of insulin gene transcription factors and incretin receptors explains, at least in part, the molecular mechanism for β-cell glucose toxicity.

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Citations

Nov 19, 2015·Journal of Molecular Endocrinology·Sumaira Z HasnainMichael McGuckin
Oct 28, 2015·Biochemical and Biophysical Research Communications·Seizo OkauchiHideaki Kaneto
Oct 25, 2017·International Journal of Environmental Research and Public Health·Demetrios PetrakisAristides M Tsatsakis
Jun 30, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Meike PaschenPer-Olof Berggren
May 10, 2019·Journal of Diabetes Investigation·Rumi FujikawaMunechika Misumi
Jul 15, 2018·Scientific Reports·Tomohiko KimuraHideaki Kaneto
Jan 1, 2016·Expert Review of Endocrinology & Metabolism·Hideaki Kaneto
Aug 24, 2017·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Tomohiko KimuraHideaki Kaneto
Apr 15, 2017·British Journal of Pharmacology·Lilla NagyPéter Bai
Oct 16, 2020·International Journal of Molecular Sciences·Olga RocheRicardo Sánchez-Prieto
Apr 4, 2021·International Journal of Molecular Sciences·Hideaki KanetoKohei Kaku
Apr 4, 2021·International Journal of Molecular Sciences·Hideaki KanetoKohei Kaku
May 30, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soo-Yeon ParkOran Kwon
Sep 24, 2019·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Li HuYan-Shan Dai

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Methods Mentioned

BETA
targeted mutation
transgenic
pancreatectomized

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