PT  - JOURNAL ARTICLE
AU  - Stoffers, D A
AU  - Kieffer, T J
AU  - Hussain, M A
AU  - Drucker, D J
AU  - Bonner-Weir, S
AU  - Habener, J F
AU  - Egan, J M
TI  - Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas.
AID  - 10.2337/diabetes.49.5.741
DP  - 2000 May 01
TA  - Diabetes
PG  - 741--748
VI  - 49
IP  - 5
4099  - http://diabetes.diabetesjournals.org/content/49/5/741.short
4100  - http://diabetes.diabetesjournals.org/content/49/5/741.full
SO  - Diabetes2000 May 01; 49
AB  - 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.