Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis

Mol Endocrinol. 2003 Feb;17(2):161-71. doi: 10.1210/me.2002-0306.


Peptide hormones are secreted from endocrine cells and neurons and exert their actions through activation of G protein-coupled receptors to regulate a diverse number of physiological systems including control of energy homeostasis, gastrointestinal motility, neuroendocrine circuits, and hormone secretion. The glucagon-like peptides, GLP-1 and GLP-2 are prototype peptide hormones released from gut endocrine cells in response to nutrient ingestion that regulate not only energy absorption and disposal, but also cell proliferation and survival. GLP-1 expands islet mass by stimulating pancreatic beta-cell proliferation and induction of islet neogenesis. GLP-1 also promotes cell differentiation, from exocrine cells or immature islet progenitors, toward a more differentiated beta-cell phenotype. GLP-2 stimulates cell proliferation in the gastrointestinal mucosa, leading to expansion of the normal mucosal epithelium, or attenuation of intestinal injury in experimental models of intestinal disease. Both GLP-1 and GLP-2 exert antiapoptotic actions in vivo, resulting in preservation of beta-cell mass and gut epithelium, respectively. Furthermore, GLP-1 and GLP-2 promote direct resistance to apoptosis in cells expressing GLP-1 or GLP-2 receptors. Moreover, an increasing number of structurally related peptide hormones and neuropeptides exert cytoprotective effects through G protein-coupled receptor activation in diverse cell types. Hence, peptide hormones, as exemplified by GLP-1 and GLP-2, may prove to be useful adjunctive tools for enhancement of cell differentiation, tissue regeneration, and cytoprotection for the treatment of human disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Exocrine Glands / cytology
  • Exocrine Glands / drug effects
  • Glucagon / pharmacology
  • Glucagon / physiology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Intestines / cytology
  • Intestines / drug effects
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Peptide Hormones / metabolism
  • Peptides / pharmacology
  • Peptides / physiology*
  • Protein Precursors / pharmacology
  • Protein Precursors / physiology*
  • Receptors, Glucagon / physiology
  • Signal Transduction


  • GLP1R protein, human
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Peptide Hormones
  • Peptides
  • Protein Precursors
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon