title: [Protective effects of glucagon-like peptide-1 on beta-cells: preclinical and clinical data].
abstract: Dipartimento di Medicina Interna e Scienze dell'Invecchiamento, Università degli Studi "G. d'Annunzio", Chieti Continuing b-cell mass and function loss represents the key mechanism for the pathogenesis and the progression of type 2 diabetes mellitus. Drugs capable of arresting b-cell loss and eventually able to bring b-cell function close to be back to normal would then be a formidable help in type 2 diabetes mellitus treatment. The glucagon-like peptide-1 (GLP-1) receptor agonists exenatide and liraglutide can stimulate in vitro neogenesis and prevent apoptosis in b-cell-like cell lines. Consistently, treatment with GLP-1 receptor agonists ameliorates glucose metabolism, preserves b-cell mass and improves b-cell function in several animal models of diabetes. For instance, in the db/db mice, liraglutide protects the b-cell from oxidative stress and endoplasmic reticulum stress-related damage. Data in humans, in vivo, are less definitive and often based on scarcely reliable indexes of b-cell function. However, short-term treatment (14 weeks) with liraglutide increased b-cell maximal response capacity in a dose-response fashion. A longer (1 year) exenatide treatment also was able to increase b-cell maximal response capacity, but the effect was no longer there after a 4-week washout period. However, a marginal, although significant as compared to glargine treatment, improvement in another b-cell function index (disposition index) was observed after a 4-week washout period following 3-year exenatide treatment. Finally, although no clinical trials with a long enough follow-up period are presently available, durable glucose control has been obtained during 2 years of liraglutide treatment in monotherapy. Since the durability of good control is strictly dependent upon a lack of further b-cell function deterioration, these clinical data may foster hope that GLP-1 receptor antagonist treatment might help preserving b-cell function also in individuals affected by type 2 diabetes mellitus.
authors.affiliation: Dipartimento di Medicina Interna e Scienze dell'Invecchiamento, Universitá egli Studi "G. d'Annunzio", Chieti. consoli@unich.it
authors.forename: Agostino
authors.initials: A
authors.lastname: Consoli
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Di Biagio
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019317:Evidence-Based Medicine; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D000069450:Liraglutide; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide