title: Clinical approaches to preserve beta-cell function in diabetes.
abstract: In type 2 diabetes (DM2) there is progressive deterioration in beta-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in beta-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the beta-cells, those to lead to short-term improvement of beta-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP 4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.
authors.affiliation: Endocrine Service and Diabetes and Heart Center of the Heart Institute, Hospital das, Clinicas of The University of São Paulo Medical School, São Paulo, SP 05403-000, Brazil. bernarwaj@globo.com
authors.forename: Bernardo Léo
authors.initials: BL
authors.lastname: Wajchenberg
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000503:physiopathology*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000069450:Liraglutide; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005947:Glucose