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Gene Review

G6pc  -  glucose-6-phosphatase, catalytic

Mus musculus

Synonyms: AW107337, G-6-Pase, G6Pase, G6pt, Glc-6-Pase, ...
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Disease relevance of G6pc


High impact information on G6pc


Chemical compound and disease context of G6pc


Biological context of G6pc


Anatomical context of G6pc

  • The longer, 1901-bp full-length cDNA encoded a 355-amino acid protein (molecular weight 40,684) structurally related (50% overall identity) to the liver glucose-6-phosphatase and exhibited similar predicted transmembrane topology, conservation of catalytically important residues, and the presence of an endoplasmic reticulum retention signal [17].
  • While G-6-Pase activity has been shown to be present in pancreatic islets, the gene responsible for this activity has not been conclusively identified [18].
  • Interestingly, although the G6Pase mRNA is expressed primarily in the liver, kidney, and intestine, the GSD-1b mRNA is expressed in numerous tissues, including human neutrophils/monocytes [1].
  • G6Pase-alpha mutants containing the beta cell antigen sequence are preferentially degraded in cells, which prevents targeting by pathogenic CD8+ T cells [19].
  • G6Pase can antagonize glucose phosphorylation, a step prerequisite in the regulation of insulin secretion from pancreatic beta cells, and G6Pase activity is increased in islets isolated from animal models of type II diabetes [20].

Associations of G6pc with chemical compounds


Physical interactions of G6pc

  • In vitro deoxyribonuclease I footprinting analyses show that the glucocorticoid receptor binds to three glucocorticoid response elements (GREs) in the -231 to -129 promoter region and transfection results indicate all three contribute to glucocorticoid induction of G6Pase gene transcription [22].
  • Mutually exclusive mutations in the G6Pase gene and the G6P transport gene establish GSD la and GSD 1b as independent molecular processes and are consistent with a multicomponent translocase catalytic model [23].

Regulatory relationships of G6pc


Other interactions of G6pc


Analytical, diagnostic and therapeutic context of G6pc


  1. Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents. Lin, B., Annabi, B., Hiraiwa, H., Pan, C.J., Chou, J.Y. J. Biol. Chem. (1998) [Pubmed]
  2. A multicomponent insulin response sequence mediates a strong repression of mouse glucose-6-phosphatase gene transcription by insulin. Streeper, R.S., Svitek, C.A., Chapman, S., Greenbaum, L.E., Taub, R., O'Brien, R.M. J. Biol. Chem. (1997) [Pubmed]
  3. Hypoglycemia and impaired hepatic glucose production in mice with a deletion of the C/EBPbeta gene. Liu, S., Croniger, C., Arizmendi, C., Harada-Shiba, M., Ren, J., Poli, V., Hanson, R.W., Friedman, J.E. J. Clin. Invest. (1999) [Pubmed]
  4. The transcription factor CCAAT/enhancer-binding protein beta regulates gluconeogenesis and phosphoenolpyruvate carboxykinase (GTP) gene transcription during diabetes. Arizmendi, C., Liu, S., Croniger, C., Poli, V., Friedman, J.E. J. Biol. Chem. (1999) [Pubmed]
  5. Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism. Taniguchi, C.M., Ueki, K., Kahn, R. J. Clin. Invest. (2005) [Pubmed]
  6. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. Combs, T.P., Berg, A.H., Obici, S., Scherer, P.E., Rossetti, L. J. Clin. Invest. (2001) [Pubmed]
  7. High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes. Haber, B.A., Chin, S., Chuang, E., Buikhuisen, W., Naji, A., Taub, R. J. Clin. Invest. (1995) [Pubmed]
  8. Dual specificity MAPK phosphatase 3 activates PEPCK gene transcription and increases gluconeogenesis in rat hepatoma cells. Xu, H., Yang, Q., Shen, M., Huang, X., Dembski, M., Gimeno, R., Tartaglia, L.A., Kapeller, R., Wu, Z. J. Biol. Chem. (2005) [Pubmed]
  9. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A., Gagne, G., Iyengar, R., Zhao, G., Marsh, K., Kym, P., Jung, P., Camp, H.S., Frevert, E. Cell metabolism. (2006) [Pubmed]
  10. Quantitative analysis of the time-dependent development of glucose-6-phosphatase-deficient foci in the livers of mice treated neonatally with diethylnitrosamine. Moore, M.R., Drinkwater, N.R., Miller, E.C., Miller, J.A., Pitot, H.C. Cancer Res. (1981) [Pubmed]
  11. Isolation of a cDNA for the catalytic subunit of rat liver glucose-6-phosphatase: regulation of gene expression in FAO hepatoma cells by insulin, dexamethasone and cAMP. Lange, A.J., Argaud, D., el-Maghrabi, M.R., Pan, W., Maitra, S.R., Pilkis, S.J. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  12. The antihyperglycemic effect of estrone sulfate in genetically obese-diabetic (ob/ob) mice is associated with reduced hepatic glucose-6-phosphatase. Borthwick, E.B., Houston, M.P., Coughtrie, M.W., Burchell, A. Horm. Metab. Res. (2001) [Pubmed]
  13. Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription. Streeper, R.S., Eaton, E.M., Ebert, D.H., Chapman, S.C., Svitek, C.A., O'Brien, R.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  14. The developmental regulation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression in the liver is partially dissociated from the control of gluconeogenesis and lipid catabolism. Yubero, P., Hondares, E., Carmona, M.C., Rossell, M., Gonzalez, F.J., Iglesias, R., Giralt, M., Villarroya, F. Endocrinology (2004) [Pubmed]
  15. Hepatocyte nuclear factor-4 alpha mediates the stimulatory effect of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) on glucose-6-phosphatase catalytic subunit gene transcription in H4IIE cells. Boustead, J.N., Stadelmaier, B.T., Eeds, A.M., Wiebe, P.O., Svitek, C.A., Oeser, J.K., O'Brien, R.M. Biochem. J. (2003) [Pubmed]
  16. WY-14,643-mediated promotion of hepatocarcinogenesis in connexin32-wild-type and connexin32-null mice. Moennikes, O., Stahl, S., Bannasch, P., Buchmann, A., Schwarz, M. Carcinogenesis (2003) [Pubmed]
  17. Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein. Arden, S.D., Zahn, T., Steegers, S., Webb, S., Bergman, B., O'Brien, R.M., Hutton, J.C. Diabetes (1999) [Pubmed]
  18. Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP). Petrolonis, A.J., Yang, Q., Tummino, P.J., Fish, S.M., Prack, A.E., Jain, S., Parsons, T.F., Li, P., Dales, N.A., Ge, L., Langston, S.P., Schuller, A.G., An, W.F., Tartaglia, L.A., Chen, H., Hong, S.B. J. Biol. Chem. (2004) [Pubmed]
  19. In islet-specific glucose-6-phosphatase-related protein, the beta cell antigenic sequence that is targeted in diabetes is not responsible for the loss of phosphohydrolase activity. Shieh, J.J., Pan, C.J., Mansfield, B.C., Chou, J.Y. Diabetologia (2005) [Pubmed]
  20. Evidence for the expression of both the hydrolase and translocase components of hepatic glucose-6-phosphatase in murine pancreatic islets. Goh, B.H., Efendić, S., Khan, A., Portwood, N. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. Bile acids regulate gluconeogenic gene expression via small heterodimer partner-mediated repression of hepatocyte nuclear factor 4 and Foxo1. Yamagata, K., Daitoku, H., Shimamoto, Y., Matsuzaki, H., Hirota, K., Ishida, J., Fukamizu, A. J. Biol. Chem. (2004) [Pubmed]
  22. The glucose-6-phosphatase catalytic subunit gene promoter contains both positive and negative glucocorticoid response elements. Vander Kooi, B.T., Onuma, H., Oeser, J.K., Svitek, C.A., Allen, S.R., Vander Kooi, C.W., Chazin, W.J., O'Brien, R.M. Mol. Endocrinol. (2005) [Pubmed]
  23. Glucose-6-phosphatase mutation G188R confers an atypical glycogen storage disease type 1b phenotype. Weston, B.W., Lin, J.L., Muenzer, J., Cameron, H.S., Arnold, R.R., Seydewitz, H.H., Mayatepek, E., Van Schaftingen, E., Veiga-da-Cunha, M., Matern, D., Chen, Y.T. Pediatr. Res. (2000) [Pubmed]
  24. Isolation of the gene for murine glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1A. Shelly, L.L., Lei, K.J., Pan, C.J., Sakata, S.F., Ruppert, S., Schutz, G., Chou, J.Y. J. Biol. Chem. (1993) [Pubmed]
  25. Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro. Metzger, S., Begleibter, N., Barash, V., Drize, O., Peretz, T., Shiloni, E., Chajek-Shaul, T. Metab. Clin. Exp. (1997) [Pubmed]
  26. Increasing fructose 2,6-bisphosphate overcomes hepatic insulin resistance of type 2 diabetes. Wu, C., Okar, D.A., Newgard, C.B., Lange, A.J. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  27. Nutrient control of phosphorylation and translocation of Foxo1 in C57BL/6 and db/db mice. Aoyama, H., Daitoku, H., Fukamizu, A. Int. J. Mol. Med. (2006) [Pubmed]
  28. Characterization of the mouse islet-specific glucose-6-phosphatase catalytic subunit-related protein gene promoter by in situ footprinting: correlation with fusion gene expression in the islet-derived betaTC-3 and hamster insulinoma tumor cell lines. Bischof, L.J., Martin, C.C., Svitek, C.A., Stadelmaier, B.T., Hornbuckle, L.A., Goldman, J.K., Oeser, J.K., Hutton, J.C., O'Brien, R.M. Diabetes (2001) [Pubmed]
  29. Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice. Burcelin, R., Kamohara, S., Li, J., Tannenbaum, G.S., Charron, M.J., Friedman, J.M. Diabetes (1999) [Pubmed]
  30. Protein kinase A phosphorylates hepatocyte nuclear factor-6 and stimulates glucose-6-phosphatase catalytic subunit gene transcription. Streeper, R.S., Hornbuckle, L.A., Svitek, C.A., Goldman, J.K., Oeser, J.K., O'Brien, R.M. J. Biol. Chem. (2001) [Pubmed]
  31. Ontogeny of the murine glucose-6-phosphatase system. Pan, C.J., Lei, K.J., Chen, H., Ward, J.M., Chou, J.Y. Arch. Biochem. Biophys. (1998) [Pubmed]
  32. Purification and characterization of mouse fetal liver epithelial cells with high in vivo repopulation capacity. Nierhoff, D., Ogawa, A., Oertel, M., Chen, Y.Q., Shafritz, D.A. Hepatology (2005) [Pubmed]
  33. In vitro differentiation and maturation of mouse embryonic stem cells into hepatocytes. Ishii, T., Yasuchika, K., Fujii, H., Hoppo, T., Baba, S., Naito, M., Machimoto, T., Kamo, N., Suemori, H., Nakatsuji, N., Ikai, I. Exp. Cell Res. (2005) [Pubmed]
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