Matches in SemOpenAlex for { <https://semopenalex.org/work/W2086158462> ?p ?o ?g. }
- W2086158462 endingPage "1245" @default.
- W2086158462 startingPage "1236" @default.
- W2086158462 abstract "Objective— Type 2 diabetes mellitus and related syndromes exhibit a deadly triad of dyslipoproteinemia, which leads to atherosclerosis; hyperglycemia, which causes microvascular disease; and hypertension. These features share a common, but unexplained, origin—namely, pathway-selective insulin resistance and responsiveness. Here, we undertook a comprehensive characterization of pathway-selective insulin resistance and responsiveness in liver and hepatocytes by examining 18 downstream targets of the insulin receptor, surveying the AKT, ERK, and NAD(P)H oxidase 4 pathways. Methods and Results— Injection of insulin into hyperphagic, obese type 2 diabetic db/db mice failed to inactivate hepatic protein tyrosine phosphatase gene family members, a crucial action of NAD(P)H oxidase 4 previously thought to be required for all signaling through AKT and ERK. Insulin-stimulated type 2 diabetic livers unexpectedly produced an unusual form of AKT that was phosphorylated at Thr308 (pT308), with only weak insulin-stimulated phosphorylation at Ser473. Remarkably, knockdown or inhibition of NAD(P)H oxidase 4 in cultured hepatocytes recapitulated the entire complicated pattern of pathway-selective insulin resistance and responsiveness seen in vivo—namely, monophosphorylated pT308-AKT, impaired insulin-stimulated pathways for lowering plasma lipids and glucose, but continued lipogenic pathways and robust ERK activation. Conclusion— Functional disturbance of a single molecule, NAD(P)H oxidase 4, is sufficient to induce the key harmful features of deranged insulin signaling in type 2 diabetes mellitus, obesity, and other conditions associated with hyperinsulinemia and pathway-selective insulin resistance and responsiveness." @default.
- W2086158462 created "2016-06-24" @default.
- W2086158462 creator A5023474681 @default.
- W2086158462 creator A5033734331 @default.
- W2086158462 date "2012-05-01" @default.
- W2086158462 modified "2023-10-05" @default.
- W2086158462 title "NOX4 Pathway as a Source of Selective Insulin Resistance and Responsiveness" @default.
- W2086158462 cites W1561326814 @default.
- W2086158462 cites W1583767403 @default.
- W2086158462 cites W1594125302 @default.
- W2086158462 cites W163006242 @default.
- W2086158462 cites W1801129364 @default.
- W2086158462 cites W1874223625 @default.
- W2086158462 cites W1964891036 @default.
- W2086158462 cites W1966190991 @default.
- W2086158462 cites W1966606518 @default.
- W2086158462 cites W1967094017 @default.
- W2086158462 cites W1967257827 @default.
- W2086158462 cites W1968171440 @default.
- W2086158462 cites W1974241409 @default.
- W2086158462 cites W1974474968 @default.
- W2086158462 cites W1975189993 @default.
- W2086158462 cites W1978370459 @default.
- W2086158462 cites W1978984304 @default.
- W2086158462 cites W1986673931 @default.
- W2086158462 cites W1989125758 @default.
- W2086158462 cites W1994096575 @default.
- W2086158462 cites W1995684078 @default.
- W2086158462 cites W1998073026 @default.
- W2086158462 cites W2000448657 @default.
- W2086158462 cites W2005112725 @default.
- W2086158462 cites W2007032642 @default.
- W2086158462 cites W2007405015 @default.
- W2086158462 cites W2009033372 @default.
- W2086158462 cites W2012297570 @default.
- W2086158462 cites W2013044317 @default.
- W2086158462 cites W2023058928 @default.
- W2086158462 cites W2032172473 @default.
- W2086158462 cites W2037813091 @default.
- W2086158462 cites W2046976278 @default.
- W2086158462 cites W2049440075 @default.
- W2086158462 cites W2051269098 @default.
- W2086158462 cites W2052550515 @default.
- W2086158462 cites W2052673116 @default.
- W2086158462 cites W2056765905 @default.
- W2086158462 cites W2067324334 @default.
- W2086158462 cites W2069700029 @default.
- W2086158462 cites W2071677256 @default.
- W2086158462 cites W2072174276 @default.
- W2086158462 cites W2075317528 @default.
- W2086158462 cites W2078281362 @default.
- W2086158462 cites W2081202575 @default.
- W2086158462 cites W2081259278 @default.
- W2086158462 cites W2084273795 @default.
- W2086158462 cites W2088024537 @default.
- W2086158462 cites W2091330563 @default.
- W2086158462 cites W2091619633 @default.
- W2086158462 cites W2094458559 @default.
- W2086158462 cites W2100718398 @default.
- W2086158462 cites W2105552847 @default.
- W2086158462 cites W2106173125 @default.
- W2086158462 cites W2106427201 @default.
- W2086158462 cites W2107674876 @default.
- W2086158462 cites W2113847169 @default.
- W2086158462 cites W2117024782 @default.
- W2086158462 cites W2117028091 @default.
- W2086158462 cites W2119210469 @default.
- W2086158462 cites W2120852510 @default.
- W2086158462 cites W2121948800 @default.
- W2086158462 cites W2122328486 @default.
- W2086158462 cites W2123890069 @default.
- W2086158462 cites W2127304691 @default.
- W2086158462 cites W2127826926 @default.
- W2086158462 cites W2131216254 @default.
- W2086158462 cites W2132302320 @default.
- W2086158462 cites W2134292324 @default.
- W2086158462 cites W2139143163 @default.
- W2086158462 cites W2150137442 @default.
- W2086158462 cites W2150225976 @default.
- W2086158462 cites W2150429576 @default.
- W2086158462 cites W2150547701 @default.
- W2086158462 cites W2153673003 @default.
- W2086158462 cites W2153747727 @default.
- W2086158462 cites W2154963552 @default.
- W2086158462 cites W2157559566 @default.
- W2086158462 cites W2158465207 @default.
- W2086158462 cites W2159504081 @default.
- W2086158462 cites W2161474086 @default.
- W2086158462 cites W2162992895 @default.
- W2086158462 cites W2166300547 @default.
- W2086158462 cites W2169632610 @default.
- W2086158462 cites W2171290692 @default.
- W2086158462 cites W2172946890 @default.
- W2086158462 cites W2337236690 @default.
- W2086158462 cites W2337454357 @default.
- W2086158462 cites W2596624061 @default.
- W2086158462 cites W2735325912 @default.
- W2086158462 cites W4238191426 @default.