title: Appropriate therapy for type 2 diabetes mellitus in view of pancreatic β-cell glucose toxicity: "the earlier, the better".
abstract: Pancreatic β-cells secrete insulin when blood glucose levels become high; however, when β-cells are chronically exposed to hyperglycemia, β-cell function gradually deteriorates, which is known as β-cell glucose toxicity. In the diabetic state, nuclear expression of the pancreatic transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) is decreased. In addition, incretin receptor expression in β-cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Clinically, it is important to select appropriate therapy for type 2 diabetes mellitus (T2DM) so that β-cell function can be preserved. In addition, when appropriate pharmacological interventions against β-cell glucose toxicity are started at the early stages of diabetes, β-cell function is substantially restored, which is not observed if treatment is started at advanced stages. These observations indicate that it is likely that downregulation of pancreatic transcription factors and/or incretin receptors is involved in β-cell dysfunction observed in T2DM and it is very important to start appropriate pharmacological intervention against β-cell glucose toxicity in the early stages of diabetes.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Obata
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shimoda
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamei
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Mune
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014157:Transcription Factors
keywords: glucose toxicity; incretin receptor; insulin gene transcription factor; 肠促胰岛素受体; 胰岛素基因转录因子; 葡萄糖毒性