Glucagon-like peptide 1(GLP-1) in biology and pathology

Diabetes Metab Res Rev. Mar-Apr 2005;21(2):91-117. doi: 10.1002/dmrr.538.

Abstract

Post-translational proteolytic processing of the preproglucagon gene in the gut results in the formation of glucagon-like peptide 1 (GLP-1). Owing to its glucose-dependent insulinotropic effect, this hormone was postulated to primarily act as an incretin, i.e. to augment insulin secretion after oral glucose or meal ingestion. In addition, GLP-1 decelerates gastric emptying and suppresses glucagon secretion. Under physiological conditions, GLP-1 acts as a part of the 'ileal brake', meaning that is slows the transition of nutrients into the distal gut. Animal studies suggest a role for GLP-1 in the development and growth of the endocrine pancreas. In light of its multiple actions throughout the body, different therapeutic applications of GLP-1 are possible. Promising results have been obtained with GLP-1 in the treatment of type 2 diabetes, but its potential to reduce appetite and food intake may also allow its use for the treatment of obesity. While rapid in vivo degradation of GLP-1 has yet prevented its broad clinical use, different pharmacological approaches aiming to extend the in vivo half-life of GLP-1 or to inhibit its inactivation are currently being evaluated. Therefore, antidiabetic treatment based on GLP-1 may become available within the next years. This review will summarize the biological effects of GLP-1, characterize its role in human biology and pathology, and discuss potential clinical applications as well as current clinical studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Gastric Inhibitory Polypeptide / chemistry
  • Gastric Inhibitory Polypeptide / physiology
  • Glucagon / blood
  • Glucagon / physiology*
  • Glucagon / therapeutic use
  • Glucagon-Like Peptide 1
  • Humans
  • Peptide Fragments / blood
  • Peptide Fragments / physiology*
  • Peptide Fragments / therapeutic use
  • Protein Precursors / blood
  • Protein Precursors / physiology*
  • Protein Precursors / therapeutic use

Substances

  • Blood Glucose
  • Peptide Fragments
  • Protein Precursors
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon