{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yoshihara E"],"funding":["NIDDK NIH HHS","NIEHS NIH HHS","NHLBI NIH HHS","NCI NIH HHS"],"pagination":["622-34"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4832237"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(4)"],"pubmed_abstract":["Pancreatic β cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal β cells. Postnatal induction of ERRγ 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 β cell-specific ERRγ expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRγ in iPSC-derived β-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 β cell-deficient mice. These results identify a key role for ERRγ in β cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human β cell therapeutics."],"journal":["Cell metabolism"],"pubmed_title":["ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells."],"pmcid":["PMC4832237"],"funding_grant_id":["R01 HL105278","R37 DK057978","R01 DK057978","HL105278","P01 HL088093","P42 ES010337","DK090962","R24 DK090962","P30 CA014195","HL088093","P30 DK063491","ES010337","DK057978"],"pubmed_authors":["Kida Y","Atkins AR","Wei Z","Dai Y","Yoshihara E","Downes M","Ahmadian M","Lin CS","Tseng T","Liddle C","Fang S","Yu RT","Evans RM"],"additional_accession":[]},"is_claimable":false,"name":"ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.","description":"Pancreatic β cells undergo postnatal maturation to achieve maximal glucose-responsive insulin secretion, an energy intensive process. We identify estrogen-related receptor γ (ERRγ) expression as a hallmark of adult, but not neonatal β cells. Postnatal induction of ERRγ 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 β cell-specific ERRγ expression are glucose intolerant and fail to secrete insulin in response to a glucose challenge. Notably, forced expression of ERRγ in iPSC-derived β-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 β cell-deficient mice. These results identify a key role for ERRγ in β cell metabolic maturation, and offer a reproducible, quantifiable, and scalable approach for in vitro generation of functional human β cell therapeutics.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Apr","modification":"2026-04-12T23:54:39.601Z","creation":"2019-03-27T02:11:35Z"},"accession":"S-EPMC4832237","cross_references":{"pubmed":["27076077"],"doi":["10.1016/j.cmet.2016.03.005"]}}