Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas
- PMID: 10905482
- DOI: 10.2337/diabetes.49.5.741
Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas
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 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.
Similar articles
-
Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats.Diabetes. 1999 Dec;48(12):2270-6. doi: 10.2337/diabetes.48.12.2270. Diabetes. 1999. PMID: 10580413
-
Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells.Endocrinology. 2002 Aug;143(8):3152-61. doi: 10.1210/endo.143.8.8973. Endocrinology. 2002. PMID: 12130581
-
Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis.J Biol Chem. 2003 Jan 3;278(1):471-8. doi: 10.1074/jbc.M209423200. Epub 2002 Oct 29. J Biol Chem. 2003. PMID: 12409292
-
Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors.Expert Opin Emerg Drugs. 2004 May;9(1):155-66. doi: 10.1517/eoed.9.1.155.32952. Expert Opin Emerg Drugs. 2004. PMID: 15155141 Review.
-
Glucagon-like peptide-1.Recent Prog Horm Res. 2001;56:377-99. doi: 10.1210/rp.56.1.377. Recent Prog Horm Res. 2001. PMID: 11237222 Review.
Cited by
-
Effect of Exendin-4 on Autophagy Clearance in Beta Cell of Rats with Tacrolimus-induced Diabetes Mellitus.Sci Rep. 2016 Jul 20;6:29921. doi: 10.1038/srep29921. Sci Rep. 2016. PMID: 27436514 Free PMC article.
-
Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to mitochondrial diabetes with progressive beta cell failure.Diabetologia. 2015 Apr;58(4):771-80. doi: 10.1007/s00125-015-3506-y. Epub 2015 Feb 8. Diabetologia. 2015. PMID: 25660120
-
Possible role of GLP-1 and its agonists in the treatment of type 1 diabetes mellitus.Curr Diab Rep. 2012 Oct;12(5):560-7. doi: 10.1007/s11892-012-0291-6. Curr Diab Rep. 2012. PMID: 22767380 Review.
-
The beneficial effects of a muscarinic agonist on pancreatic β-cells.Sci Rep. 2019 Nov 7;9(1):16180. doi: 10.1038/s41598-019-52691-8. Sci Rep. 2019. PMID: 31700039 Free PMC article.
-
Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors.J Clin Invest. 2004 Feb;113(4):635-45. doi: 10.1172/JCI20518. J Clin Invest. 2004. PMID: 14966573 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical