Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sensing of peripheral hormones and nutrients by the hypothalamus plays an important role in maintaining peripheral glucose homeostasis. The hormone resistin impairs the response to insulin in liver and other peripheral tissues. Here we demonstrate that in normal mice resistin delivered in the lateral cerebral ventricle increased endogenous glucose production during hyperinsulinemic-euglycemic clamp, consistent with induction of hepatic insulin resistance. In agreement, central resistin inhibited Akt phosphorylation and increased the expression of glucose-6-phosphatase, the enzyme regulating glucose output in the liver. Central resistin induced expression of proinflammatory cytokines as well as suppressor of cytokine signaling-3, a negative regulator of insulin action in liver. Central infusion of resistin was associated with neuronal activation in the arcuate, paraventricular and dorsomedial nuclei, and increased neuropeptide Y (NPY) expression in the hypothalamus. The effects of central resistin on glucose production as well as hepatic expression of proinflammatory cytokines were abrogated in mice lacking NPY. Pretreatment of wild-type mice with antagonists of the NPY Y1 receptor, but not the Y5 receptor, also prevented the effects of central resistin. Together, these results suggest that resistin action on NPY neurons is an important regulator of hepatic insulin sensitivity.
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PMID:Central resistin induces hepatic insulin resistance via neuropeptide Y. 1803 66

The regulation of expression of gluconeogenic genes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver plays an important role in glucose homeostasis, because aberrant expression of these genes contributes to the development of type 2 diabetes. Previous reports demonstrate that signal transducer and activator of transcription 3 (STAT3) plays a key role in regulating gluconeogenic gene expression, but the mechanism remains unclear. Herein we demonstrate that phosphorylated STAT3 is required for repression of G6Pase expression by IL-6 in both HepG2 cells and mouse liver. Interestingly, PEPCK expression is regulated by STAT3 independent of IL-6 activation. Using in vivo chromatin immunoprecipitation, we demonstrate that STAT3 binds to the promoters of the G6Pase, PEPCK, and suppressor of cytokine signaling (SOCS)3 genes, and its recruitment increases at the G6Pase and SOCS3 promoters with IL-6 treatment. Whereas persistent recruitment of RNA polymerase II is seen on the SOCS3 promoter, consistent with its induction by IL-6, a decrease in polymerase II recruitment and histone H4 acetylation is seen at the G6Pase promoter with IL-6 treatment. Thus STAT3 mediates negative regulation of hepatic gluconeogenic gene expression in vivo by interacting with regulatory regions of these genes.
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PMID:STAT3 targets the regulatory regions of gluconeogenic genes in vivo. 1926 44