{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:17:49Z","timestamp":1791328669336,"version":"4.3.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2011,3,21]],"date-time":"2011-03-21T00:00:00Z","timestamp":1300665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A bone-pancreas endocrine loop has been identified recently that involves insulin secreted from \u03b2-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 \u03b2-cells. The identity of the Ocn-sensing receptor in \u03b2-cells is a missing component of this endocrine loop. The abnormalities in glucose homeostasis in Gprc6a null mice suggests that this pertussis toxin\u2013sensitive G protein\u2013coupled 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\u2009cells with a full-length Gprc6a cDNA imparted a dose-dependent response to Ocn (5 to 60\u2009ng\/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 \u03b2-cell line. Ocn also stimulated ERK activity in TC-6 pancreatic \u03b2-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\u2212\/\u2212 mice. These findings suggest that GPRC6A is a candidate for mediating the response to Ocn in the bone-pancreas endocrine loop regulating insulin signaling. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.390","type":"journal-article","created":{"date-parts":[[2011,3,21]],"date-time":"2011-03-21T20:42:25Z","timestamp":1300740145000},"page":"1680-1683","source":"Crossref","is-referenced-by-count":205,"title":["GPRC6A mediates responses to osteocalcin in \u03b2-cells in vitro and pancreas in vivo"],"prefix":"10.1093","volume":"26","author":[{"given":"Min","family":"Pi","sequence":"first","affiliation":[{"name":"Musculoskeletal, Orthopedic and Dental Institute and Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Musculoskeletal, Orthopedic and Dental Institute and Department of 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