title: Nutrient regulation of pancreatic beta-cell function in diabetes: problems and potential solutions.
abstract: Increasing prevalence of obesity combined with longevity will produce an epidemic of Type 2 (non-insulin-dependent) diabetes in the next 20 years. This disease is associated with defects in insulin secretion, specifically abnormalities of insulin secretory kinetics and pancreatic beta-cell glucose responsiveness. Mechanisms underlying beta-cell dysfunction include glucose toxicity, lipotoxicity and beta-cell hyperactivity. Defects at various sites in beta-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent studies highlight diverse beta-cell actions of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These intestinal hormones target the beta-cell to stimulate glucose-dependent insulin secretion through activation of protein kinase A and associated pathways. Both increase gene expression and proinsulin biosynthesis, protect against apoptosis and stimulate replication/neogenesis of beta-cells. Incretin hormones therefore represent an exciting future multi-action solution to correct beta-cell defect in Type 2 diabetes.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK. pr.flatt@ulster.ac.uk
authors.forename: P R
authors.initials: PR
authors.lastname: Flatt
authors.forename: B D
authors.initials: BD
authors.lastname: Green
mesh_terms: D000595:Amino Acid Sequence; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism; D005502:Food; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008969:Molecular Sequence Data
chemical_list: D018819:Dipeptidyl Peptidase 4