Clinical approaches to preserve beta-cell function in diabetes

Adv Exp Med Biol. 2010;654:515-35. doi: 10.1007/978-90-481-3271-3_23.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / physiopathology*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Liraglutide
  • Models, Biological
  • PPAR gamma / metabolism
  • Thiazolidinediones / pharmacology

Substances

  • Insulin
  • PPAR gamma
  • Thiazolidinediones
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Glucose