Evolving Concepts in Incretin Action

Alan D. Cherrington, PhD
Laurie Baggio PhD
Michael Nauck, MD
Tracy Anne Perry, PhD

Reviewed by Joelle Escoffery, PhD

This symposium addressed the evolving role of incretin hormones.  The incretin effect refers to the observed 3-fold increase in insulin and C-peptide when glucose is delivered orally, as compared with intravenously. A series of studies in dogs demonstrated that glucose delivered via the portal vein augments the role of the liver in glucose uptake and decreases the role of the periphery. Further, glucagon-like peptide-1 (GLP-1) administered portally creates a significant increase in hepatic glucose uptake. GLP-1 has important implications for type 2 diabetes, as it increases insulin secretion, suppresses glucagon secretion, increases satiety, and may also increase β-cell mass and decrease β-cell apoptosis. As GLP-1 receptors are present in the hypothalamus, GLP-1 may also demonstrate neuroprotective effects in terms of stroke. Although GLP-1 has important implications for the treatment of type 2 diabetes, naturally-occurring GLP-1 cannot be used therapeutically due to the proteolytic action of dipeptidyl peptidase-IV (DPP-IV). However, alternative approaches to GLP-1 delivery are being investigated, including using substrates that mimic GLP-1 such as exenatide; binding to albumin to increase half-life, as is the case for liraglutide and CJC-1311.