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

Doris A. Stoffers, Timothy J. Kieffer, Mehboob A. Hussain, Daniel J. Drucker, Susan Bonner-Weir, Joel F. Habener, Josephine M. Egan

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-cells that produce insulin. Mature β-cells have a lifespan of ~48-56 days (rat) and are replaced by the replication of preexisting β-cells and by the differentiation and proliferation of new β-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 β-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 β-cell neogenesis and may thereby be an effective treatment for diabetes.

Original languageEnglish (US)
Pages (from-to)741-748
Number of pages8
JournalDiabetes
Volume49
Issue number5
DOIs
StatePublished - May 2000

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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