(Journal Article): New Therapeutic Strategies for the Treatment of Type 2 Diabetes Mellitus Based on Incretins
 
Gallwitz B (Department of Medicine IV, Eberhard-Karls-University, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany, baptist.gallwitz(at)med.uni-tuebingen.de )
 
IN: Rev Diabetic Stud 2005; 2(2):61-69
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

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ABSTRACT: Orally ingested glucose leads to a greater insulin response compared to intravenously administered glucose leading to identical postprandial plasma glucose excursions, a phenomenon referred to as the "incretin effect". The incretin effect comprises up to 60% of the postprandial insulin secretion and is diminished in type 2 diabetes. One of the very important gastrointestinal hormones promoting this effect is glucagon-like peptide 1 (GLP-1). It only stimulates insulin secretion and normalizes blood glucose in humans under hyperglycemic conditions, therefore it does not cause hypoglycemia. Other important physiological actions of GLP-1 are the inhibition of glucagon secretion and gastric emptying. It further acts as a neurotransmitter in the hypothalamus stimulating satiety. In vitro and animal data demonstrated that GLP-1 increases β-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. In humans, the improvement of β-cell function can be indirectly observed from the increased insulin secretory capacity after GLP-1 infusions. GLP-1 represents an attractive therapeutic principle for type 2 diabetes. However, native GLP-1 is degraded rapidly upon exogenous administration and is therefore not feasible for routine therapy. The first long-acting GLP-1 analog ("incretin mimetic") Exenatide (Byetta®) has just been approved for type 2 diabetes therapy. Other compounds are being investigated in clinical trials (e.g. liraglutide®, CJC1131®). Dipeptidyl-peptidase IV inhibitors (DPP-IV inhibitors; e.g. Vildagliptin®, Sitagliptin®) that inhibit the enzyme responsible for incretin degradation are also under study.

TYPE OF PUBLICATION: Review

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