2,659 research outputs found

    The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H\u3csub\u3e2\u3c/sub\u3e0\u3csub\u3e2\u3c/sub\u3e and plays an integral role in insulin signal transduction

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    Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H2O2 generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action

    On the sensitivity of FPGA architectural conclusions to experimental assumptions, tools, and techniques

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    Understanding the Gap between Website Value and Consumer Shopping Orientation: An Application of Task-Technology Fit Theory to Online shopping Values

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    Value judgments, such as functional, emotional, utilitarian, and hedonic values have received considerable attention in recent years. However, research on these interrelationships has been somewhat limited in online shopping, particularly in regards to the gap between website values versus consumer shopping orientations. The purpose of this research is to propose and empirically test a conceptual framework that incorporates the interrelationships of website values, shopping satisfaction, and repurchase intention into framework and validate them in a B2C online shopping context. Specifically, we examine the moderating role of consumer shopping orientations in the impact of website values on shopping satisfaction. Our results suggest that the impact of website values on shopping satisfaction is negatively moderated by consumer shopping orientations. Therefore, functional and emotional values are probably necessary but are an insufficient precondition for cultivating shopping satisfaction. Moreover, consumer hedonic orientation plays a slightly higher influence on shopping satisfaction than utilitarian orientation. Understanding these factors can provide direction for planning website features as well as consumer desired values that will increase shopping satisfaction and repurchase intention
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