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Diabetes 53:S197-S204, 2004
© 2004 by the American Diabetes Association, Inc.

Section V: The Incretin Pathway

The Incretin Approach for Diabetes Treatment

Modulation of Islet Hormone Release by GLP-1 Agonism

Jens Juul Holst, and Cathrine Ørskov

From the Departments of Medical Physiology and Medical Anatomy, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

Glucagon-like peptide (GLP)-1 is a gut hormone that stimulates insulin secretion, gene expression, and ß-cell growth. Together with the related hormone glucose-dependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect, the augmentation of insulin secretion after oral as opposed to intravenous administration of glucose. Type 2 diabetic patients typically have little or no incretin-mediated augmentation of insulin secretion. This is due to decreased secretion of GLP-1 and loss of the insulinotropic effects of GIP. GLP-1, however, retains insulinotropic effects, and the hormone effectively improves metabolism in patients with type 2 diabetes. Continuous subcutaneous administration greatly improved glucose profiles and lowered body weight and HbA1c levels. Further, free fatty acid levels were lowered, insulin resistance was improved, and ß-cell performance was greatly improved. The natural peptide is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPP IV), but resistant analogs as well as inhibitors of DPP IV are now under development, and both approaches have shown remarkable efficacy in experimental and clinical studies.

Address correspondence and reprint requests to Jens Juul Holst, MD, Departments of Medical Physiology and Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark. E-mail: holst{at}mfi.ku.dk


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.