Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 296, Issue 1, Pages E174-E181Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.90419.2008
Keywords
glucagon; glucagon-like peptide-1; exchange protein directly activated by adenosine 3 ',5 '-cyclic monophosphate; protein kinase A
Categories
Funding
- Canadian Diabetes Association [2341, 2374]
- Canadian Institute of Health Research [79534]
- Juvenile Diabetes Research Foundation [1-2005-1112]
- Canada Research Chairs Program
- Banting and Best Diabetes Centre-Novo Nordisk
Ask authors/readers for more resources
Islam D, Zhang N, Wang P, Li H, Brubaker PL, Gaisano HY, Wang Q, Jin T. Epac is involved in cAMP-stimulated proglucagon expression and hormone production but not hormone secretion in pancreatic alpha- and intestinal L-cell lines. Am J Physiol Endocrinol Metab 296: E174-E181, 2009. First published October 14, 2008; doi: 10.1152/ajpendo.90419.2008.-Both Epac and PKA are effectors of the second messenger cAMP. Utilizing an exchange protein directly activated by cAMP ( Epac) pathway-specific cAMP analog (ESCA), we previously reported that Epac signaling regulates proglucagon gene (gcg) expression in the glucagon-like peptide-1 (GLP-1)producing intestinal endocrine L-cell lines GLUTag and STC-1. We now show that Epac-2 is also expressed in glucagon-producing pancreatic alpha-cell lines, including PKA-deficient InR1-G9 cells, and that ESCA stimulates gcg promoter and mRNA expression in the InR1-G9 cells. Using a dominant-negative Epac-2 expression plasmid (Epac-2DN), we found that Epac inhibition attenuated forskolin-stimulated gcg promoter expression in the PKA-active STC-1 cell line and blocked forskolin-stimulated gcg promoter expression in the InR1-G9 cells. Consistently, ESCA was shown to stimulate glucagon and GLP-1 production in the InR1-G9 and GLUTag cell lines, respectively. Surprisingly, ESCA treatment did not show a notable stimulation of glucagon or GLP-1 secretion from these two cell lines. This is in contrast to its ability to stimulate insulin secretion from the pancreatic INS-1 beta-cell line. Our findings suggest that Epac is selectively involved in peptide hormone secretion in pancreatic and intestinal endocrine cells and that distinct signaling cascades are involved in stimulating production vs. secretion of glucagon and GLP-1 in response to cAMP elevation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available