Novel Insights Into the Regulation of Postprandial Lipemia by Glucagon-Like Peptides: Significance for Diabetes

  1. Dick C. Chan
  1. School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia
  1. Corresponding author: Gerald F. Watts, gerald.watts{at}uwa.edu.au.

Glucagon-like peptide-1 (GLP-1) and GLP-2 are peptide hormones encoded by the proglucagon gene that are cosecreted in equimolar amounts from enteroendocrine L-cells of the intestine in response to nutrients, primarily carbohydrates and fats (1). Most is known about GLP-1, which stimulates the pancreatic secretion of insulin in a glucose-dependent manner while inhibiting the secretion of glucagon, gastric emptying, and satiety. This tonic effect maintains glucose homeostasis and is chiefly controlled by the enzymatic degradation of the peptide in the circulation by dipeptidyl peptidase-4 (DPP-4) (2). This has led to the development of new therapies for diabetes, including GLP-1 receptor analogs and inhibitors of DPP-4 (3).

By contrast to GLP-1, the physiological and therapeutic roles of GLP-2 are less clear. GLP-2 inhibits postprandial gastric motility/secretion and intestinal hexose transport and has a trophic effect on intestinal epithelium that implies a specific role in intestinal repair processes (4). GLP-2 may antagonize the effects of GLP-1 on glucose homeostasis by enhancing the pancreatic release of glucagon but could also have a cooperative, short-term effect on satiety. Its biological actions are mediated by a specific G-protein–coupled receptor.

Recent studies have also suggested that GLP-1 and possibly GLP-2 may be involved in regulating fat absorption and chylomicron biogenesis (58), pointing to a regulatory role in postprandial lipid metabolism. This has implications for atherogenesis and vascular disease in diabetes and insulin-resistant states. GLP-1 may improve while GLP-2 may aggravate postprandial lipemia, but exactly how these biological actions are intertwined in health and disease remains unclear.

In this issue of Diabetes, Adeli and colleagues …

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