New insights into the role of cAMP in the production and function of the incretin hormone glucagon-like peptide-1 (GLP-1).
The proglucagon gene (gcg) encodes both glucagon and glucagon-like peptide-1 (GLP-1), produced in pancreatic alpha cells and intestinal endocrine L cells, respectively. The incretin hormone GLP-1 stimulates insulin secretion and pro-insulin gene transcription. GLP-1 also enhances pancreatic beta-cell proliferation, inhibits cell apoptosis, and has been utilized in the trans-differentiation of insulin producing cells. A long-term effective GLP-1 receptor agonist, Byetta, has now been developed as the drug in treating type II diabetes and potentially other metabolic disorders. The expression of gcg and the production of GLP-1 can be activated by the elevation of the second messenger cyclic AMP (cAMP). Recent studies suggest that in addition to protein kinase A (PKA), exchange protein activated by cAMP (Epac), another effector of cAMP, and the crosstalk between PKA and the Wnt signaling pathway, are involved in cAMP-stimulated gcg transcription and GLP-1 production as well. Finally, functions of GLP-1 in pancreatic beta cells are also mediated by PKA, Epac, as well as the effector of the Wnt signaling pathway. Together, these novel findings bring us a new insight into the role of cAMP in the production and function of the incretin hormone GLP-1.
Yu
Zhiwen
Z
Banting and Best Diabetes Centre, University of Toronto, Canada.
Jin
Tianru
T
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D054795:Incretins; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt