title: Pancreatic β-cell glucose toxicity in type 2 diabetes mellitus.
abstract: Pancreatic β-cells secrete insulin when blood glucose levels become high. However, when β-cells are chronically exposed to hyperglycemia, their function gradually deteriorates. Although such phenomena are called as β-cell glucose toxicity, its molecular mechanism remained unclear. This manuscript describes the possible mechanism for such β-cell dysfunction. In the diabetic state, nuclear expression levels of pancreatic transcription factors PDX-1 and MafA are decreased. In addition, incretin receptor expression in β- cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Taken together, it is likely that down-regulation of pancreatic transcription factors and/or incretin receptors are involved in β-cell dysfunction observed in type 2 diabetes.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan. kaneto@med.kawasaki-m.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology; D051473:Maf Transcription Factors, Large / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose