Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas

Diabetes. 2000 May;49(5):741-8. doi: 10.2337/diabetes.49.5.741.


Diabetes is caused by a failure of the pancreas to produce insulin in amounts sufficient to meet the body's needs. A hallmark of diabetes is an absolute (type 1) or relative (type 2) reduction in the mass of pancreatic beta-cells that produce insulin. Mature beta-cells have a lifespan of approximately 48-56 days (rat) and are replaced by the replication of preexisting beta-cells and by the differentiation and proliferation of new beta-cells (neogenesis) derived from the pancreatic ducts. Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. GLP-1 also enhances beta-cell neogenesis and islet size. Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / physiopathology
  • Exenatide
  • Glucagon / agonists*
  • Glucagon-Like Peptide 1
  • Homeodomain Proteins*
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / growth & development*
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Peptide Fragments / agonists*
  • Peptides / pharmacology
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / physiology
  • Protein Precursors / agonists*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Venoms*


  • Homeodomain Proteins
  • Insulin
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Trans-Activators
  • Venoms
  • pancreatic and duodenal homeobox 1 protein
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide