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Gene Review

Gck  -  glucokinase

Rattus norvegicus

Synonyms: GLUKA, Glucokinase, HK IV, HK4, Hexokinase type IV, ...
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Disease relevance of Gck

  • An alternate splice acceptor site in the 4th exon of the glucokinase gene was identified in two glucokinase cDNAs from rat insulinoma tissue [1].
  • Glucose phosphorylating activity increased by up to 20-fold in extracts from islets treated with adenoviruses containing the cDNAs encoding either tissue isoform of glucokinase, but such cells exhibited no increase in 2- or 5-[3H]glucose usage, lactate production, glycogen content, or glucose oxidation [2].
  • Finally, GK expression was increased in rats with impaired central glucosensing (posthypoglycemia and diet-induced obesity) but was unaffected by a 48-h fast [3].
  • The introduction of the glucokinase transgene in insulin receptor null mice did not prevent the development of glycosuria [4].
  • Similar promoter activity was also detected in dRLh-84 hepatoma cells, which do not express glucokinase [5].

Psychiatry related information on Gck


High impact information on Gck


Chemical compound and disease context of Gck


Biological context of Gck


Anatomical context of Gck


Associations of Gck with chemical compounds

  • The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte [16].
  • Dual role of phosphofructokinase-2/fructose bisphosphatase-2 in regulating the compartmentation and expression of glucokinase in hepatocytes [23].
  • To understand the role of GK in glucoprivic counterregulatory responses, we injected alloxan, a GK inhibitor and toxin, into the third ventricle (3v) to target nearby GK-expressing neurons [24].
  • We detected a cDNA encoding the precursor of propionyl-CoA carboxylase beta subunit (pbetaPCCase), and glutathione S-transferase pull-down assay illustrated that pbetaPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts [21].
  • Furthermore, glucokinase overexpression enhanced insulin secretion in response to stimulatory glucose or glucose plus arginine by only 36-53% relative to control islets [2].

Physical interactions of Gck

  • Despite normal to elevated hexokinase and glucokinase activities in the islets of these glucose-intolerant animals and despite normal mitochondrial binding of the hexokinase isoenzymes, the metabolic response to a high concentration of D-glucose is severely affected, especially in terms of D-[6-14C]glucose oxidation [25].

Regulatory relationships of Gck

  • Hepatic glucokinase is inhibited by a 68-kDa glucokinase regulatory protein (GKRP) that is expressed in molar excess [16].
  • Substrates and glucagon induced adaptive changes in the mitochondrial glucokinase/GKRP ratio suggesting a regulatory role for GKRP [26].
  • In the fasted state, a 3 fold glucokinase overexpression was sufficient to mimic feeding-induced increases in pyruvate kinase and acetyl CoA carboxylase mRNA levels, demonstrating a primary role for glucose metabolism in the regulation of these genes in vivo [27].
  • A reconstituted system prepared from RINm5F and HIT cell extracts exhibited a composite concentration-dependency curve of glucose usage and showed substantial inhibition of hexokinase and almost fully expressed glucokinase [28].
  • Amylin proved ineffective in suppressing subsequent accumulation of glucokinase mRNA in response to maximal or submaximal doses of insulin [29].

Other interactions of Gck


Analytical, diagnostic and therapeutic context of Gck

  • Asparagine-leucine motifs of glucokinase located in the hinge region, as well as in the large domain, were changed by site-directed mutagenesis [33].
  • Northern blot reveals that fasting levels of Gck expression are reduced after programming, although this distinction disappears after feeding [19].
  • The mRNA levels of glucokinase and of its regulatory protein decreased rapidly after partial hepatectomy to minimum values at 6 hours (15%) and at 12 hours (4%), respectively, returning to normal values at 24 hours and 168 hours, respectively [34].
  • GK mRNA was also found in the area postrema/nucleus tractus solitarius region by RT-PCR [3].
  • Using the bDNA assay, a sensitive signal amplification technique, we detected relative increases in glucokinase messenger RNA levels of 40.5 +/- 7.5% after 3-h incubation with cAMP [35].


  1. An alternate promoter in the glucokinase gene is active in the pancreatic beta cell. Magnuson, M.A., Shelton, K.D. J. Biol. Chem. (1989) [Pubmed]
  2. Differential effects of overexpressed glucokinase and hexokinase I in isolated islets. Evidence for functional segregation of the high and low Km enzymes. Becker, T.C., Noel, R.J., Johnson, J.H., Lynch, R.M., Hirose, H., Tokuyama, Y., Bell, G.I., Newgard, C.B. J. Biol. Chem. (1996) [Pubmed]
  3. Glucokinase is the likely mediator of glucosensing in both glucose-excited and glucose-inhibited central neurons. Dunn-Meynell, A.A., Routh, V.H., Kang, L., Gaspers, L., Levin, B.E. Diabetes (2002) [Pubmed]
  4. Improved metabolic disorders of insulin receptor-deficient mice by transgenic overexpression of glucokinase in the liver. Jackerott, M., Baudry, A., Bucchini, D., Jami, J., Joshi, R.L. Diabetologia (2002) [Pubmed]
  5. Characterization of the 5' flanking region of rat glucokinase gene. Noguchi, T., Takenaka, M., Yamada, K., Matsuda, T., Hashimoto, M., Tanaka, T. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  6. Enzymes of carbohydrate metabolism in young and adult rats fed diets differing in fat and carbohydrate. Brooks, S.P., Lampi, B.J. Mol. Cell. Biochem. (1996) [Pubmed]
  7. Effect of glycerol on glucokinase activity: loss of cooperative behavior with respect to glucose. Pollard-Knight, D., Connolly, B.A., Cornish-Bowden, A., Trayer, I.P. Arch. Biochem. Biophys. (1985) [Pubmed]
  8. Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation. Burns, S.P., Desai, M., Cohen, R.D., Hales, C.N., Iles, R.A., Germain, J.P., Going, T.C., Bailey, R.A. J. Clin. Invest. (1997) [Pubmed]
  9. Glucokinase and cytosolic phosphoenolpyruvate carboxykinase (GTP) in the human liver. Regulation of gene expression in cultured hepatocytes. Iynedjian, P.B., Marie, S., Gjinovci, A., Genin, B., Deng, S.P., Buhler, L., Morel, P., Mentha, G. J. Clin. Invest. (1995) [Pubmed]
  10. In situ glucose uptake and glucokinase activity of pancreatic islets in diabetic and obese rodents. Liang, Y., Bonner-Weir, S., Wu, Y.J., Berdanier, C.D., Berner, D.K., Efrat, S., Matschinsky, F.M. J. Clin. Invest. (1994) [Pubmed]
  11. Regulatory effects of glucose on the catalytic activity and cellular content of glucokinase in the pancreatic beta cell. Study using cultured rat islets. Chen, C., Hosokawa, H., Bumbalo, L.M., Leahy, J.L. J. Clin. Invest. (1994) [Pubmed]
  12. Glucokinase and glucokinase regulatory protein: mutual dependence for nuclear localization. Bosco, D., Meda, P., Iynedjian, P.B. Biochem. J. (2000) [Pubmed]
  13. Identification of glucokinase as an alloxan-sensitive glucose sensor of the pancreatic beta-cell. Meglasson, M.D., Burch, P.T., Berner, D.K., Najafi, H., Matschinsky, F.M. Diabetes (1986) [Pubmed]
  14. Glucosamine-induced inhibition of liver glucokinase impairs the ability of hyperglycemia to suppress endogenous glucose production. Barzilai, N., Hawkins, M., Angelov, I., Hu, M., Rossetti, L. Diabetes (1996) [Pubmed]
  15. Effect of thyroid hormones on glucokinase gene transcription in rat liver. Höppner, W., Seitz, H.J. J. Biol. Chem. (1989) [Pubmed]
  16. The role of the regulatory protein of glucokinase in the glucose sensory mechanism of the hepatocyte. de la Iglesia, N., Mukhtar, M., Seoane, J., Guinovart, J.J., Agius, L. J. Biol. Chem. (2000) [Pubmed]
  17. Liver glucokinase can be activated by peroxisome proliferator-activated receptor-gamma. Kim, S.Y., Kim, H.I., Park, S.K., Im, S.S., Li, T., Cheon, H.G., Ahn, Y.H. Diabetes (2004) [Pubmed]
  18. Insulin regulation of glucokinase gene expression: evidence against a role for sterol regulatory element binding protein 1 in primary hepatocytes. Gregori, C., Guillet-Deniau, I., Girard, J., Decaux, J.F., Pichard, A.L. FEBS Lett. (2006) [Pubmed]
  19. Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming. Bogdarina, I., Murphy, H.C., Burns, S.P., Clark, A.J. Life Sci. (2004) [Pubmed]
  20. Rat glucokinase gene: structure and regulation by insulin. Magnuson, M.A., Andreone, T.L., Printz, R.L., Koch, S., Granner, D.K. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  21. A novel glucokinase regulator in pancreatic beta cells: precursor of propionyl-CoA carboxylase beta subunit interacts with glucokinase and augments its activity. Shiraishi, A., Yamada, Y., Tsuura, Y., Fijimoto, S., Tsukiyama, K., Mukai, E., Toyoda, Y., Miwa, I., Seino, Y. J. Biol. Chem. (2001) [Pubmed]
  22. Characterization of glucokinase-binding protein epitopes by a phage-displayed peptide library. Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel interaction partner. Baltrusch, S., Lenzen, S., Okar, D.A., Lange, A.J., Tiedge, M. J. Biol. Chem. (2001) [Pubmed]
  23. Dual role of phosphofructokinase-2/fructose bisphosphatase-2 in regulating the compartmentation and expression of glucokinase in hepatocytes. Payne, V.A., Arden, C., Wu, C., Lange, A.J., Agius, L. Diabetes (2005) [Pubmed]
  24. Third ventricular alloxan reversibly impairs glucose counterregulatory responses. Sanders, N.M., Dunn-Meynell, A.A., Levin, B.E. Diabetes (2004) [Pubmed]
  25. Impairment of the mitochondrial oxidative response to D-glucose in pancreatic islets from adult rats injected with streptozotocin during the neonatal period. Giroix, M.H., Sener, A., Bailbe, D., Portha, B., Malaisse, W.J. Diabetologia (1990) [Pubmed]
  26. Glucokinase regulatory protein is associated with mitochondria in hepatocytes. Arden, C., Baltrusch, S., Agius, L. FEBS Lett. (2006) [Pubmed]
  27. A modest glucokinase overexpression in the liver promotes fed expression levels of glycolytic and lipogenic enzyme genes in the fasted state without altering SREBP-1c expression. Scott, D.K., Collier, J.J., Doan, T.T., Bunnell, A.S., Daniels, M.C., Eckert, D.T., O'Doherty, R.M. Mol. Cell. Biochem. (2003) [Pubmed]
  28. Control of glucose metabolism in pancreatic beta-cells by glucokinase, hexokinase, and phosphofructokinase. Model study with cell lines derived from beta-cells. Shimizu, T., Parker, J.C., Najafi, H., Matschinsky, F.M. Diabetes (1988) [Pubmed]
  29. Unimpaired effect of insulin on glucokinase gene expression in hepatocytes challenged with amylin. Nouspikel, T., Gjinovci, A., Li, S., Iynedjian, P.B. FEBS Lett. (1992) [Pubmed]
  30. Role of the insulin receptor substrate 1 and phosphatidylinositol 3-kinase signaling pathway in insulin-induced expression of sterol regulatory element binding protein 1c and glucokinase genes in rat hepatocytes. Matsumoto, M., Ogawa, W., Teshigawara, K., Inoue, H., Miyake, K., Sakaue, H., Kasuga, M. Diabetes (2002) [Pubmed]
  31. Activation of protein kinase B/cAkt in hepatocytes is sufficient for the induction of expression of the gene encoding glucokinase. Iynedjian, P.B., Roth, R.A., Fleischmann, M., Gjinovci, A. Biochem. J. (2000) [Pubmed]
  32. Peroxisomal proliferator-activated receptor-gamma upregulates glucokinase gene expression in beta-cells. Kim, H.I., Cha, J.Y., Kim, S.Y., Kim, J.W., Roh, K.J., Seong, J.K., Lee, N.T., Choi, K.Y., Kim, K.S., Ahn, Y.H. Diabetes (2002) [Pubmed]
  33. Interaction of glucokinase with the liver regulatory protein is conferred by leucine-asparagine motifs of the enzyme. Baltrusch, S., Francini, F., Lenzen, S., Tiedge, M. Diabetes (2005) [Pubmed]
  34. Gene expression of glucokinase regulatory protein in regenerating rat liver. Rosa, J.L., Pérez, J.X., Detheux, M., Van Schaftingen, E., Bartrons, R. Hepatology (1997) [Pubmed]
  35. Cyclic adenosine 3',5'-monophosphate increases pancreatic glucokinase activity and gene expression. Fernandez-Mejia, C., Vega-Allende, J., Rojas-Ochoa, A., Rodriguez-Dorantes, M., Romero-Navarro, G., Matschinsky, F.M., Wang, J., German, M.S. Endocrinology (2001) [Pubmed]
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