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

• Main Authors: Hideaki Kaneto, Taka-aki Matsuoka
• Format: Article
• Language: English
• Published: MDPI AG 2015-03-01
• Series: International Journal of Molecular Sciences
• Subjects: pancreatic β-cells; oxidative stress; PDX-1; MafA; GLP-1
• Online Access: http://www.mdpi.com/1422-0067/16/3/6281

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.