| First Author | Porat S | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 4 | Pages | 440-449 |
| PubMed ID | 21459328 | Mgi Jnum | J:172243 |
| Mgi Id | MGI:5005034 | Doi | 10.1016/j.cmet.2011.02.012 |
| Citation | Porat S, et al. (2011) Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab 13(4):440-9 |
| abstractText | Recent studies revealed a surprising regenerative capacity of insulin-producing beta cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic beta cell regeneration under stressed conditions relies on accelerated proliferation of surviving beta cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that beta cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in beta cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory beta cell proliferation in vivo. Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces beta cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of K(ATP) channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of beta cell mass by metabolic demand. |
