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)

Insulin inhibits the expression of the hepatic insulin-like growth factor-binding protein-1 (IGFBP-1) and glucose-6-phosphatase (G6Pase) genes. The signaling pathway that mediates these events requires the activation of phosphatidylinositol 3-kinase, whereas transfection studies have suggested an involvement of Akt (protein kinase B) and FKHR, a transcription factor regulated by Akt. We now demonstrate that insulin repression of endogenous IGFBP-1 gene transcription was blocked by rapamycin or by amino acid starvation. Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin, whereas amino acid depletion prevented insulin induction of these signaling molecules. Importantly, we demonstrate that insulin regulation of the thymine-rich insulin response element of the IGFBP-1 promoter was also inhibited by rapamycin. However, sustained activation of S6K1 did not repress this promoter. In addition, rapamycin did not affect insulin regulation of G6Pase expression or Akt activation. We propose that these observations indicate that an mTOR-dependent, but S6K-independent mechanism regulates the suppression of IGFBP-1 (but not G6Pase) gene expression by insulin. Therefore, although the insulin-responsive sequence of the G6Pase gene promoter is related to that of the IGFBP-1 promoter, the signaling pathways that mediate suppression of these genes are distinct.
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PMID:Insulin regulation of insulin-like growth factor-binding protein-1 gene expression is dependent on the mammalian target of rapamycin, but independent of ribosomal S6 kinase activity. 1178 21

Genetic selection is commonly used in farm animals to manage body fat content. In rainbow trout, divergent selection for low or high muscle fat content leads to differences in utilization of dietary energy sources between the fat muscle line (FL) and the lean muscle line (LL). To establish whether genetic selection on muscle fat content affects the hepatic insulin/nutrient signaling pathway, we analyzed this pathway and the expression of several metabolism-related target genes in the livers of the two divergent lines under fasting and then refeeding conditions. Whereas glycemia returned to basal level 24 h after refeeding in FL trout, it remained elevated in the LL trout. Target of rapamycin (TOR) protein was more abundant in the livers of FL trout than in LL trout, and refeeding activation of the hepatic TOR signaling pathway (TOR, S6K1, and S6) was therefore enhanced. Genes related to glycolysis (glucokinase and pyruvate kinase) and gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) were only slightly affected by refeeding and genetic selection. Refeeding stimulated expression of lipogenic genes and the sterol-responsive element binding protein (SREBP1), and expression of fatty acid synthase, glucose-6-phosphate dehydrogenase, and serine dehydratase was predominant in the livers of FL fish compared with LL fish. In agreement with recent findings linking TOR to lipogenesis control, we concluded that genetic selection for muscle fat content resulted in overactivation of the TOR signaling pathway-associated lipogenesis and probably also improved utilization of glucose.
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PMID:Rainbow trout genetically selected for greater muscle fat content display increased activation of liver TOR signaling and lipogenic gene expression. 1971 Mar 90