Endocrine Index Glossary

Enteroglucagon and Glucagon-Like Peptides

Glucagon is best known as a peptide hormone secreted from pancreatic islets that participates in control of glucose metabolism. Glucagon is synthesized initially as the protein proglucagon, which, in mammals, is encoded by a single gene. Within alpha cells of the pancreas, proglucagon is processed by proteolytic cleavage into glucagon itself, and several biologically inactive peptides.

Interestingly, the proglucagon gene is also expressed in the terminal small intestine and large intestine, where it is cleaved into a number of peptides other than glucagon. This alternative pathway for processing of proglucagon occurs in gut endocrinocytes called L cells. Because these peptides were discovered by cross reactions with antisera against glucagon, they were originally given the name "enteroglucagon", and are sometimes referred to collectively as "proglucagon-derived peptides".

The major, characterized patterns of proglucagon processing are depicted in the figure below. In both pancreas and gut, three types of products are generated:

  • Peptides with known biological activity (yellow color): glucagon and glucagon-like peptide-1 (GLP-1)
  • Peptides that may have biological activity, but which are poorly characterized or active only at what are considered non-physiologic concentrations (cyan color): glucagon-like peptide-2 (GLP-2) and oxyntomodulin
  • Peptides without apparent biological activity(gray color): glicentin, glicentin-related pancreatic peptide, major proglucagon fragment.

Regardless of activity, each of these peptides is secreted into blood after ingestion of a meal containing carbohydrates or lipids.

Glucagon-like peptide-1 has a major effect of enhancing the release of insulin in response to a glucose stimulus, and coincidentally, suppressing secretion of glucagon. As a result, injections of this hormone lower blood glucose levels, not only in normal people, but in those having insulin-dependent and non-insulin-dependent diabetes mellitus. For this reason, GLP-1 is being investigated for its utility in the therapy of diabetes.

GLP-1 has been shown to potently inhibit several aspects of digestive function, including gastric emptying, gastric secretion and pancreatic secretion. Like many gut peptides, GLP-1 is also synthesized in the brain, and may play a role in control of food intake.

Glucagon-like peptide-2 is not well characterized, but some reports suggest that it stimulates proliferation of intestinal epithelial cells.

Oxyntomodulin is identical to glucagon, but with an 8 amino acid extension on the C-terminus. Experimentally, it has glucagon-like activity, but this is of doubtful physiologic significance, as it binds the glucagon receptor with low affinity relative to glucagon. Other effects that have been demonstrated include inhibition of gastric secretion and motility, and inhibition of pancreatic secretion.

References and Reviews

  • Ahren B: Glucagon-like peptide-1 (GLP-1): a gut hormone of potential interest in the treatment of diabetes. Bioessays 20:642-651, 1998.
  • Drucker DJ: Glucagon-like peptides. Diabetes 47:159-169, 1998.
  • Holst JJ: Enteroglucagon. Annu Rev Physiol 59:257-271, 1997.

Index of: Gastrointestinal Hormones

Last updated on January 24, 1999
Author: R. Bowen
Send comments via form or email to rbowen@colostate.edu