| First Author | Wei J | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 3 | Pages | 1021-31 |
| PubMed ID | 24009262 | Mgi Jnum | J:208919 |
| Mgi Id | MGI:5565394 | Doi | 10.2337/db13-0887 |
| Citation | Wei J, et al. (2014) Osteocalcin promotes beta-cell proliferation during development and adulthood through Gprc6a. Diabetes 63(3):1021-31 |
| abstractText | Expanding beta-cell mass through beta-cell proliferation is considered a potential therapeutic approach to treat beta-cell failure in diabetic patients. A necessary step toward achieving this goal is to identify signaling pathways that regulate beta-cell proliferation in vivo. Here we show that osteocalcin, a bone-derived hormone, regulates beta-cell replication in a cyclin D1-dependent manner by signaling through the Gprc6a receptor expressed in these cells. Accordingly, mice lacking Gprc6a in the beta-cell lineage only are glucose intolerant due to an impaired ability to produce insulin. Remarkably, this regulation occurs during both the perinatal peak of beta-cell proliferation and in adulthood. Hence, the loss of osteocalcin/Gprc6a signaling has a profound effect on beta-cell mass accrual during late pancreas morphogenesis. This study extends the endocrine role of osteocalcin to the developmental period and establishes osteocalcin/Gprc6a signaling as a major regulator of beta-cell endowment that can become a potential target for beta-cell proliferative therapies. |
