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Int. J. Mol. Sci. 2015, 16(3), 6281-6297; doi:10.3390/ijms16036281

Role of Pancreatic Transcription Factors in Maintenance of Mature β-Cell Function

1
Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan
2
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Florian Lang
Received: 16 December 2014 / Revised: 10 February 2015 / Accepted: 16 February 2015 / Published: 18 March 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [570 KB, uploaded 18 March 2015]   |  

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. View Full-Text
Keywords: pancreatic β-cells; oxidative stress; PDX-1; MafA; GLP-1 pancreatic β-cells; oxidative stress; PDX-1; MafA; GLP-1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kaneto, H.; Matsuoka, T.-A. Role of Pancreatic Transcription Factors in Maintenance of Mature β-Cell Function. Int. J. Mol. Sci. 2015, 16, 6281-6297.

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