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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
Int. J. Mol. Sci. 2015, 16(3), 6281-6297; https://doi.org/10.3390/ijms16036281
Received: 16 December 2014 / Revised: 10 February 2015 / Accepted: 16 February 2015 / Published: 18 March 2015
(This article belongs to the Section Biochemistry)
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
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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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