Clinical approaches to preserve beta-cell function in diabetes.
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.
Wajchenberg
Bernardo Léo
BL
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
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
D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005947:Glucose