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Incretin-based therapies – review of the physiology, pharmacology and emerging clinical experience

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Abstract

Diabetes therapies based on manipulation of the incretin system are now widely available, with millions of people receiving treatment. The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4-resistant peptides that bind to and activate the glucagon-like peptide-1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.
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Keywords: DPP4; GIP; GLP-1; incretin; type 2 diabetes

Document Type: Research Article

Affiliations: 1: Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Bledamsvej, Copenhagen, Denmark 2: A.W. Morrow Gastroenterology and Liver Centre and Associate Faculty Centenary Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales 3: Mater Medical Research Institute and Professor of Endocrinology, University of Queensland, Brisbane, Australia

Publication date: 01 April 2011

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