The Promise of Incretin Therapies: Acute Improvement and Long-term Preservation of Islet Cell Function

Corporate-sponsored Symposium
Supported by an unrestricted educational grant from Novartis Pharmaceuticals Corporation
Friday, June 10, 2005
6:00-9:00 PM

Chair:
Steven Kahn, ChB

Faculty:
David D’Alessio, MD
Daniel J Drucker, MD, FRCP, FACP

Reported by Joelle Escoffery, PhD

The incretin hormones, which are secreted by endocrine cells in the intestinal mucosa, play an important role in glucose homeostasis. Two primary incretins have been identified: glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1). GIP may play a role in lipid metabolism. GLP-1 has a number of beneficial effects in people with type 2 diabetes, including stimulation of glucose-dependent insulin secretion, suppression of glucagon secretion, delay of gastric emptying, and beta-cell stimulation.

GLP-1 has been shown to exert a number of beneficial effects on the beta cell. Specifically, administration of GLP-1 increases beta-cell mass in rodents and decreases apoptosis in both rodents and freshly-isolated human islets. Conversely, blocking GLP-1 is associated with reduced islet cell regeneration in rodent models.

Because native GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), therapeutic approaches to GLP-1 enhancement have taken on 2 forms: the identification of GLP-1 receptor agonists that are resistant to DPP-4 or inhibiting DPP-4. The GLP-1 receptor agonists exenatide and liraglutide have been shown to improve glycemic control and suppress glucagon secretion. DPP-4 inhibitors have been shown to improve glycemic control and suppress glucagon secretion. Further, DPP-4 inhibititors have a synergistic effect with metformin for the improvement of glycemic control.