| http://purl.uniprot.org/citations/20440072 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20440072 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that regulates cellular stress responses. While the levels of HIF-1alpha protein are tightly regulated, recent studies suggest that it can be active under normoxic conditions. We hypothesized that HIF-1alpha is required for normal beta cell function and reserve and that dysregulation may contribute to the pathogenesis of type 2 diabetes (T2D). Here we show that HIF-1alpha protein is present at low levels in mouse and human normoxic beta cells and islets. Decreased levels of HIF-1alpha impaired glucose-stimulated ATP generation and beta cell function. C57BL/6 mice with beta cell-specific Hif1a disruption (referred to herein as beta-Hif1a-null mice) exhibited glucose intolerance, beta cell dysfunction, and developed severe glucose intolerance on a high-fat diet. Increasing HIF-1alpha levels by inhibiting its degradation through iron chelation markedly improved insulin secretion and glucose tolerance in control mice fed a high-fat diet but not in beta-Hif1a-null mice. Increasing HIF-1alpha levels markedly increased expression of ARNT and other genes in human T2D islets and improved their function. Further analysis indicated that HIF-1alpha was bound to the Arnt promoter in a mouse beta cell line, suggesting direct regulation. Taken together, these findings suggest an important role for HIF-1alpha in beta cell reserve and regulation of ARNT expression and demonstrate that HIF-1alpha is a potential therapeutic target for the beta cell dysfunction of T2D."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci35846"xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Cheng K."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Kahn C.R."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Okada T."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Scott C."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Gonzalez F.J."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Wang X.L."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Yim S.H."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "O'Connell P.J."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Ho K."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Kulkarni R.N."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Lau S.M."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Gunton J.E."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Laybutt D.R."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Hawthorne W.J."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Biankin A.V."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Loudovaris T."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Shah Y."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Kay T.W."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Kench J.G."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Grey S.T."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/author | "Stokes R."xsd:string |
| http://purl.uniprot.org/citations/20440072 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |