Send to:

Choose Destination
See comment in PubMed Commons below
J Endocrinol. 2010 Sep;206(3):261-9. doi: 10.1677/JOE-10-0030. Epub 2010 Jun 11.

Pancreas-specific Gsalpha deficiency has divergent effects on pancreatic alpha- and beta-cell proliferation.

Author information

  • 1Signal Transduction Section, Metabolic Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.


The ubiquitously expressed G protein alpha-subunit G(s)alpha mediates the intracellular cAMP response to glucagon-like peptide 1 (GLP1) and other incretin hormones in pancreatic islet cells. We have shown previously that mice with beta-cell-specific G(s)alpha deficiency (betaGsKO) develop severe early-onset insulin-deficient diabetes with a severe defect in beta-cell proliferation. We have now generated mice with G(s)alpha deficiency throughout the whole pancreas by mating G(s)alpha-floxed mice with Pdx1-cre transgenic mice (PGsKO). PGsKO mice also developed severe insulin-deficient diabetes at a young age, confirming the important role of G(s)alpha signaling in beta-cell growth and function. Unlike in betaGsKO mice, islets in PGsKO mice had a relatively greater proportion of alpha-cells, which were spread throughout the interior of the islet. Similar findings were observed in mice with pancreatic islet cell-specific G(s)alpha deficiency using a neurogenin 3 promoter-cre recombinase transgenic mouse line. Studies in the alpha-cell line alphaTC1 confirmed that reduced cAMP signaling increased cell proliferation while increasing cAMP produced the opposite effect. Therefore, it appears that G(s)alpha/cAMP signaling has opposite effects on pancreatic alpha- and beta-cell proliferation, and that impaired GLP1 action in alpha- and beta-cells via G(s)alpha signaling may be an important contributor to the reciprocal effects on insulin and glucagon observed in type 2 diabetics. In addition, PGsKO mice show morphological changes in exocrine pancreas and evidence for malnutrition and dehydration, indicating an important role for G(s)alpha in the exocrine pancreas as well.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk