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

International Journal of Molecular Sciences

Hideaki Kaneto²  Taka-aki Matsuoka¹ 

[1] Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; E-Mail:;Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan

关键词: pancreatic β-cells;    oxidative stress;    PDX-1;    MafA;    GLP-1;   

DOI  :  10.3390/ijms16036281

来源: mdpi

【 摘 要 】

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 β-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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.