FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2077103634> ?p ?o ?g. }

• W2077103634 endingPage "1337" @default.
• W2077103634 startingPage "1331" @default.
• W2077103634 abstract "In two separate studies, Amato Giaccia and Calvin Kuo and colleagues show that targeting of hypoxia-inducible factor-2α to increase its expression results in elevation of a key downstream effector of insulin signaling and thus improved insulin sensitivity in a mouse model of type 2 diabetes. Insulin initiates diverse hepatic metabolic responses, including gluconeogenic suppression and induction of glycogen synthesis and lipogenesis1,2. The liver possesses a rich sinusoidal capillary network with a higher degree of hypoxia and lower gluconeogenesis in the perivenous zone as compared to the rest of the organ3. Here, we show that diverse vascular endothelial growth factor (VEGF) inhibitors improved glucose tolerance in nondiabetic C57BL/6 and diabetic db/db mice, potentiating hepatic insulin signaling with lower gluconeogenic gene expression, higher glycogen storage and suppressed hepatic glucose production. VEGF inhibition induced hepatic hypoxia through sinusoidal vascular regression and sensitized liver insulin signaling through hypoxia-inducible factor-2α (Hif-2α, encoded by Epas1) stabilization. Notably, liver-specific constitutive activation of HIF-2α, but not HIF-1α, was sufficient to augment hepatic insulin signaling through direct and indirect induction of insulin receptor substrate-2 (Irs2), an essential insulin receptor adaptor protein4,5,6. Further, liver Irs2 was both necessary and sufficient to mediate Hif-2α and Vegf inhibition effects on glucose tolerance and hepatic insulin signaling. These results demonstrate an unsuspected intersection between Hif-2α−mediated hypoxic signaling and hepatic insulin action through Irs2 induction, which can be co-opted by Vegf inhibitors to modulate glucose metabolism. These studies also indicate distinct roles in hepatic metabolism for Hif-1α, which promotes glycolysis7,8,9, and Hif-2α, which suppresses gluconeogenesis, and suggest new treatment approaches for type 2 diabetes mellitus." @default.
• W2077103634 created "2016-06-24" @default.
• W2077103634 creator A5000271359 @default.
• W2077103634 creator A5015053419 @default.
• W2077103634 creator A5025336530 @default.
• W2077103634 creator A5025422656 @default.
• W2077103634 creator A5039425117 @default.
• W2077103634 creator A5040611860 @default.
• W2077103634 creator A5043656144 @default.
• W2077103634 creator A5044095800 @default.
• W2077103634 creator A5048055596 @default.
• W2077103634 creator A5049548894 @default.
• W2077103634 creator A5054580964 @default.
• W2077103634 creator A5054812572 @default.
• W2077103634 creator A5056685479 @default.
• W2077103634 creator A5057258274 @default.
• W2077103634 creator A5060648910 @default.
• W2077103634 creator A5062471285 @default.
• W2077103634 creator A5064938640 @default.
• W2077103634 creator A5071823933 @default.
• W2077103634 creator A5079075847 @default.
• W2077103634 creator A5080172191 @default.
• W2077103634 creator A5085499922 @default.
• W2077103634 creator A5086540456 @default.
• W2077103634 date "2013-09-15" @default.
• W2077103634 modified "2023-10-11" @default.
• W2077103634 title "A liver Hif-2α–Irs2 pathway sensitizes hepatic insulin signaling and is modulated by Vegf inhibition" @default.
• W2077103634 cites W1965247049 @default.
• W2077103634 cites W1967364108 @default.
• W2077103634 cites W1969750989 @default.
• W2077103634 cites W1972460996 @default.
• W2077103634 cites W1978021683 @default.
• W2077103634 cites W1980725734 @default.
• W2077103634 cites W1988377666 @default.
• W2077103634 cites W1992888159 @default.
• W2077103634 cites W1995856733 @default.
• W2077103634 cites W1998493448 @default.
• W2077103634 cites W2000292756 @default.
• W2077103634 cites W2001658518 @default.
• W2077103634 cites W2005195518 @default.
• W2077103634 cites W2012461219 @default.
• W2077103634 cites W2012652496 @default.
• W2077103634 cites W2013655374 @default.
• W2077103634 cites W2021548432 @default.
• W2077103634 cites W2035286393 @default.
• W2077103634 cites W2036496650 @default.
• W2077103634 cites W2044257922 @default.
• W2077103634 cites W2050830271 @default.
• W2077103634 cites W2061342616 @default.
• W2077103634 cites W2066089681 @default.
• W2077103634 cites W2067324334 @default.
• W2077103634 cites W2070009707 @default.
• W2077103634 cites W2070254655 @default.
• W2077103634 cites W2084697100 @default.
• W2077103634 cites W2093044616 @default.
• W2077103634 cites W2095793094 @default.
• W2077103634 cites W2098417675 @default.
• W2077103634 cites W2105669313 @default.
• W2077103634 cites W2105925116 @default.
• W2077103634 cites W2106129165 @default.
• W2077103634 cites W2109560454 @default.
• W2077103634 cites W2132272301 @default.
• W2077103634 cites W2142622000 @default.
• W2077103634 cites W2144137526 @default.
• W2077103634 cites W2144718958 @default.
• W2077103634 cites W2147160899 @default.
• W2077103634 cites W2162187216 @default.
• W2077103634 cites W2162352067 @default.
• W2077103634 cites W2168865951 @default.
• W2077103634 cites W2196957880 @default.
• W2077103634 doi "https://doi.org/10.1038/nm.3295" @default.
• W2077103634 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3795838" @default.
• W2077103634 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24037094" @default.
• W2077103634 hasPublicationYear "2013" @default.
• W2077103634 type Work @default.
• W2077103634 sameAs 2077103634 @default.
• W2077103634 citedByCount "86" @default.
• W2077103634 countsByYear W20771036342013 @default.
• W2077103634 countsByYear W20771036342014 @default.
• W2077103634 countsByYear W20771036342015 @default.
• W2077103634 countsByYear W20771036342016 @default.
• W2077103634 countsByYear W20771036342017 @default.
• W2077103634 countsByYear W20771036342018 @default.
• W2077103634 countsByYear W20771036342019 @default.
• W2077103634 countsByYear W20771036342020 @default.
• W2077103634 countsByYear W20771036342021 @default.
• W2077103634 countsByYear W20771036342022 @default.
• W2077103634 countsByYear W20771036342023 @default.
• W2077103634 crossrefType "journal-article" @default.
• W2077103634 hasAuthorship W2077103634A5000271359 @default.
• W2077103634 hasAuthorship W2077103634A5015053419 @default.
• W2077103634 hasAuthorship W2077103634A5025336530 @default.
• W2077103634 hasAuthorship W2077103634A5025422656 @default.
• W2077103634 hasAuthorship W2077103634A5039425117 @default.
• W2077103634 hasAuthorship W2077103634A5040611860 @default.
• W2077103634 hasAuthorship W2077103634A5043656144 @default.
• W2077103634 hasAuthorship W2077103634A5044095800 @default.
• W2077103634 hasAuthorship W2077103634A5048055596 @default.

• next