| First Author | Yoshihara E | Year | 2016 |
| Journal | Cell Metab | Volume | 23 |
| Issue | 4 | Pages | 622-34 |
| PubMed ID | 27076077 | Mgi Jnum | J:235402 |
| Mgi Id | MGI:5796239 | Doi | 10.1016/j.cmet.2016.03.005 |
| Citation | Yoshihara E, et al. (2016) ERRgamma Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive beta Cells. Cell Metab 23(4):622-34 |
| abstractText | Pancreatic beta cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor gamma (ERRgamma) expression as a hallmark of adult, but not neonatal beta cells. Postnatal induction of ERRgamma drives a transcriptional network activating mitochondrial oxidative phosphorylation, the electron transport chain, and ATP production needed to drive glucose-responsive insulin secretion. Mice deficient in beta cell-specific ERRgamma expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRgamma in iPSC-derived beta-like cells enables glucose-responsive secretion of human insulin in vitro, obviating in vivo maturation to achieve functionality. Moreover, these cells rapidly rescue diabetes when transplanted into beta cell-deficient mice. These results identify a key role for ERRgamma in beta cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human beta cell therapeutics. |
