Glucagon-like peptide-1 as a treatment option for type 2 diabetes and its role in restoring beta-cell mass.
The "incretin effect" describes the enhanced insulin response from orally ingested glucose compared with intravenous glucose leading to identical postprandial plasma glucose excursions. It makes up to 60% of the postprandial insulin secretion but is diminished in type 2 diabetes. Gastrointestinal hormones promoting the incretin effect are called incretins. Glucagon-like peptide- 1 (GLP-1) is an important incretin. In vitro and animal data have demonstrated that GLP-1 increases beta-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. The improvement of beta-cell function can be indirectly observed from the increased insulin secretory capacity of humans receiving GLP-1 or incretin mimetics that act like GLP-1. Furthermore, GLP-1 inhibits glucagon secretion and rarely causes hypoglycemia. It may represent an attractive therapeutic method for type 2 diabetes because of its multiple effects, including a slowing of gastric emptying and the simulation of satiety by acting as a transmitter in the CNS. Native GLP-1 is degraded rapidly upon intravenous or subcutaneous administration and is therefore not feasable for routine therapy. Long-acting GLP-1 analogs (e.g., Liraglutide [Novo Nordisk, Copenhagen, Denmark]) and exenadin-4 (Exenatide [Eli Lilly, Indianapolis, IN]) that are resistant to degradation, called "incretin mimetics," are being investigated in clinical trials. Dipeptidyl peptidase IV inhibitors (e.g., Vildagliptin [Novartis, Basel, Switzerland]) that inhibit the enzyme responsible for incretin degradation are also under study.
Gallwitz
B
B
Department of Medicine IV, Eberhard-Karls-University, Otfried-Müller-Strasse 10, D-72076 Tübingen, Germany. baptist.gallwitz@med.uni-tuebingen.de
D000595:Amino Acid Sequence; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005934:Glucagon / Q000737:chemistry / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D011498:Protein Precursors / Q000737:chemistry / Q000627:therapeutic use*; D012527:Satiation
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon