Open AccessDown-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes
Author(s) -
Hideaki Kaneto,
Takaaki Matsuoka
Publication year - 2013
Publication title -
world journal of diabetes
Language(s) - English
Resource type - Journals
ISSN - 1948-9358
DOI - 10.4239/wjd.v4.i6.263
Subject(s) - incretin , endocrinology , medicine , receptor , diabetes mellitus , type 2 diabetes , transcription factor , oxidative stress , biology , gene , biochemistry
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.