title: [Progress in diabetes].
abstract: Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic beta-cell failure. Pancreatic beta-cell failure plays an important role in the pathogenesis of diabetes in Japanese subjects. Several mechanisms underlying the causes of pancreatic beta-cell failure have been reported, including decreased insulin signaling, endoplasmic reticulum stress, oxidative stress, and inflammation. In addition, the role of epigenetics in this association has recently been highlighted. Intrauterine growth retardation (IUGR) leads to many disorders after maturation, such as obesity, glucose intolerance, and osteoporosis. IUGR also reduces pancreatic / cell mass. One of the underlying mechanisms is epigenetic modification, such as the reduction of histone acetylation and increase of methylation in the promoter region of the Pdx1 gene, which encodes an important transcription factor for pancreatic beta-cell function, leading to the reduction of Pdx1 expression levels. Numerous susceptibility genes for type 2 diabetes, including KCNQ1, have been identified in humans using genome-wide analyses and other related studies. The Kcnq1 locus is an imprinting gene. Noncoding RNA Kcnq1ot1 is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced expression of Kcnqlot1 as well as increased expression of Cdkn1c, an imprinted gene that encodes a cell cycle inhibitor only when the mutation is on the paternal allele. Furthermore, histone modification in the Cdkn1c promoter region in pancreatic islets was found to contribute to this phenomenon. These results indicate that epigenetic modification might be important for the regulation of pancreatic beta-cell mass and the onset of diabetes.
authors.affiliation: Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan. kido@med.kobe-u.ac.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kido
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D007328:Insulin