Paper Report for: Gallwitz_2005_Rev.Diabet.Stud_2_61
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Title: New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins Gallwitz B Ref: Rev Diabet Stud, 2:61, 2005 : PubMed
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 beta-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. In humans, the improvement of beta-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.
        
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Gallwitz B (2005) New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins Rev Diabet Stud2: 61-9