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World J Diabetes. Dec 15, 2013; 4(6): 263-269
Published online Dec 15, 2013. doi: 10.4239/wjd.v4.i6.263
Down-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes
Hideaki Kaneto, Taka-aki Matsuoka
Hideaki Kaneto, Taka-aki Matsuoka, Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
Author contributions: Kaneto H and Matsuoka TA wrote the paper.
Correspondence to: Hideaki Kaneto, MD, PhD, Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@endmet.med.osaka-u.ac.jp
Telephone: +81-6-68793743 Fax: +81-6-68793739
Received: August 26, 2013
Revised: October 26, 2013
Accepted: November 15, 2013
Published online: December 15, 2013
Processing time: 115 Days and 22.2 Hours
Abstract

Type 2 diabetes is one of the most prevalent and serious metabolic diseases. Under diabetic conditions, chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreatic β-cell function, which leads to the aggravation of type 2 diabetes. Although such phenomena are well known as glucose toxicity, its molecular mechanism remains unclear. In this review article, we describe the possible molecular mechanism for β-cell dysfunction found in type 2 diabetes, focusing on (1) oxidative stress, (2) pancreatic transcription factors (PDX-1 and MafA) and (3) incretin receptors (GLP-1 and GIP receptors). Under such conditions, nuclear expression levels of PDX-1 and MafA are decreased, which leads to suppression of insulin biosynthesis and secretion. In addition, expression levels of GLP-1 and GIP receptors are decreased, which likely contributes to the impaired incretin effects found in diabetes. Taken together, it is likely that down-regulation of pancreatic transcription factors (PDX-1 and MafA) and down-regulation of incretin receptors (GLP-1 and GIP receptors) explain, at least in part, the molecular mechanism for β-cell dysfunction found in type 2 diabetes.

Keywords: Pancreatic β-cells; Oxidative stress; Pancreatic duodenal homeobox-1; MafA; Incretin receptor

Core tip: Expression of pancreatic transcription factors and incretin receptors is decreased in diabetes.