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J Bone Miner Res. 2011 Jul;26(7):1680-3. doi: 10.1002/jbmr.390.

GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo.

Author information

1
Musculoskeletal, Orthopedic and Dental Institute and Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. mpi@uthsc.edu

Abstract

A bone-pancreas endocrine loop has been identified recently that involves insulin secreted from β-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 β-cells. The identity of the Ocn-sensing receptor in β-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 β-cell line. Ocn also stimulated ERK activity in TC-6 pancreatic β-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.

PMID:
21425331
PMCID:
PMC5079536
DOI:
10.1002/jbmr.390
[Indexed for MEDLINE]
Free PMC Article

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