Down-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes

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.