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

Diabetes is caused by a failure of the pancreas to produce insulin in amoun ts sufficient to meet the body's needs. A hallmark of diabetes is an absolu te (type 1) or relative (type 2) reduction in the mass of pancreatic beta-c ells that produce insulin, Mature beta-cells have a lifespan of similar to 48-56 days (rat) and are replaced by the replication of preexisting beta-ce lls and by the differentiation and proliferation of new beta-cells (neogene sis) derived from the pancreatic ducts. Here, we show that the insulinotrop ic hormone glucagon-like peptide (GLP)-1, which is produced by the intestin e, enhances the pancreatic expression of the homeodomain transcription fact or IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. Concomitantly, GLP-1 administered to diabet ic mice stimulates insulin secretion and effectively lowers their blood sug ar levels. GLP-1 also enhances beta-cell neogenesis and islet size. Thus, i n addition to stimulating insulin secretion, GLP-1 stimulates the expressio n of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes.