Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 26, Issue 7, Pages 1680-1683Publisher
WILEY-BLACKWELL
DOI: 10.1002/jbmr.390
Keywords
GPRC6A; OSTEOCALCIN RECEPTOR; GPCR; INSULIN; PANCREATIC beta CELLS
Categories
Funding
- Amgen
- Genzyme
- Servier
- VasoGenix
- NIH [R01-AR37308]
Ask authors/readers for more resources
A bone-pancreas endocrine loop has been identified recently that involves insulin secreted from beta-cells in the pancreas stimulating insulin receptors in osteoblasts, leading to osteoblastic differentiation and increased secretion of osteocalcin (Ocn), a bone-derived hormone that regulates insulin secretion in beta-cells. The identity of the Ocn-sensing receptor in beta-cells is a missing component of this endocrine loop. The abnormalities in glucose homeostasis in Gprc6a null mice suggests that this pertussis toxin-sensitive G protein-coupled receptor is a candidate for mediating the effects of Ocn on insulin secretion in the pancreas. In support of this possibility, we found that transfection of non-Gprc6a-expressing HEK-293 cells with a full-length Gprc6a cDNA imparted a dose-dependent response to Ocn (5 to 60 ng/mL), as measured by PKD1 and ERK phosphorylation. In addition, Gprc6a is highly expressed in mouse pancreatic tissue and in the mouse TC-6 pancreatic beta-cell line. Ocn also stimulated ERK activity in TC-6 pancreatic beta-cells. Finally, intraperitoneal injection of Ocn stimulated ERK activity in the pancreas and increased serum insulin levels in wild-type mice, but these responses were markedly attenuated in Gprc6a(-/-) mice. These findings suggest that GPRC6A is a candidate for mediating the response to Ocn in the bone-pancreas endocrine loop regulating insulin signaling. (C) 2011 American Society for Bone and Mineral Research.
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