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. 2004 Mar 1;378(Pt 2):693–697. doi: 10.1042/BJ20031414

Differences in regulatory properties between human and rat glucokinase regulatory protein.

Katy J Brocklehurst 1, Rick A Davies 1, Loranne Agius 1
PMCID: PMC1223974  PMID: 14627435

Abstract

The inhibition of glucokinase by rat and Xenopus GKRPs (glucokinase regulatory protein) is well documented. We report a comparison of the effects of human and rat GKRPs on glucokinase activity. Human GKRP is a more potent inhibitor of glucokinase than rat GKRP in the absence of fructose 6-phosphate or sorbitol 6-phosphate, and has a higher affinity for these ligands. However, human and rat GKRPs have similar affinities for fructose 1-phosphate and chloride. Residues that are not conserved between the rodent and human proteins affect both the affinity for fructose 6-phosphate and sorbitol 6-phosphate and the inhibitory potency of GKRP on glucokinase in the absence of these ligands.

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Selected References

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  1. Alvarez Elvira, Roncero Isabel, Chowen Julie A., Vázquez Patricia, Blázquez Enrique. Evidence that glucokinase regulatory protein is expressed and interacts with glucokinase in rat brain. J Neurochem. 2002 Jan;80(1):45–53. doi: 10.1046/j.0022-3042.2001.00677.x. [DOI] [PubMed] [Google Scholar]
  2. Detheux M., Vandercammen A., Van Schaftingen E. Effectors of the regulatory protein acting on liver glucokinase: a kinetic investigation. Eur J Biochem. 1991 Sep 1;200(2):553–561. doi: 10.1111/j.1432-1033.1991.tb16218.x. [DOI] [PubMed] [Google Scholar]
  3. Hawkins Meredith, Gabriely Ilan, Wozniak Robert, Vilcu Cristian, Shamoon Harry, Rossetti Luciano. Fructose improves the ability of hyperglycemia per se to regulate glucose production in type 2 diabetes. Diabetes. 2002 Mar;51(3):606–614. doi: 10.2337/diabetes.51.3.606. [DOI] [PubMed] [Google Scholar]
  4. Hayward B. E., Dunlop N., Intody S., Leek J. P., Markham A. F., Warner J. P., Bonthron D. T. Organization of the human glucokinase regulator gene GCKR. Genomics. 1998 Apr 1;49(1):137–142. doi: 10.1006/geno.1997.5195. [DOI] [PubMed] [Google Scholar]
  5. Matschinsky F. M. Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes. Diabetes. 1990 Jun;39(6):647–652. doi: 10.2337/diab.39.6.647. [DOI] [PubMed] [Google Scholar]
  6. Matschinsky Franz M. Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes. 2002 Dec;51 (Suppl 3):S394–S404. doi: 10.2337/diabetes.51.2007.s394. [DOI] [PubMed] [Google Scholar]
  7. Mookhtiar K. A., Kalinowski S. S., Brown K. S., Tsay Y. H., Smith-Monroy C., Robinson G. W. Heterologous expression and characterization of rat liver glucokinase regulatory protein. Diabetes. 1996 Dec;45(12):1670–1677. doi: 10.2337/diab.45.12.1670. [DOI] [PubMed] [Google Scholar]
  8. Moore M. C., Cherrington A. D., Mann S. L., Davis S. N. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. J Clin Endocrinol Metab. 2000 Dec;85(12):4515–4519. doi: 10.1210/jcem.85.12.7053. [DOI] [PubMed] [Google Scholar]
  9. Moore M. C., Davis S. N., Mann S. L., Cherrington A. D. Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes. Diabetes Care. 2001 Nov;24(11):1882–1887. doi: 10.2337/diacare.24.11.1882. [DOI] [PubMed] [Google Scholar]
  10. Van Schaftingen E. A protein from rat liver confers to glucokinase the property of being antagonistically regulated by fructose 6-phosphate and fructose 1-phosphate. Eur J Biochem. 1989 Jan 15;179(1):179–184. doi: 10.1111/j.1432-1033.1989.tb14538.x. [DOI] [PubMed] [Google Scholar]
  11. Vandercammen A., Van Schaftingen E. Competitive inhibition of liver glucokinase by its regulatory protein. Eur J Biochem. 1991 Sep 1;200(2):545–551. doi: 10.1111/j.1432-1033.1991.tb16217.x. [DOI] [PubMed] [Google Scholar]
  12. Vandercammen A., Van Schaftingen E. Species and tissue distribution of the regulatory protein of glucokinase. Biochem J. 1993 Sep 1;294(Pt 2):551–556. doi: 10.1042/bj2940551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Vandercammen A., Van Schaftingen E. The mechanism by which rat liver glucokinase is inhibited by the regulatory protein. Eur J Biochem. 1990 Jul 31;191(2):483–489. doi: 10.1111/j.1432-1033.1990.tb19147.x. [DOI] [PubMed] [Google Scholar]
  14. Veiga-Da-Cunha M., Detheux M., Watelet N., Van Schaftingen E. Cloning and expression of a Xenopus liver cDNA encoding a fructose-phosphate-insensitive regulatory protein of glucokinase. Eur J Biochem. 1994 Oct 1;225(1):43–51. doi: 10.1111/j.1432-1033.1994.00043.x. [DOI] [PubMed] [Google Scholar]
  15. Veiga-da-Cunha M., Delplanque J., Gillain A., Bonthron D. T., Boutin P., Van Schaftingen E., Froguel P. Mutations in the glucokinase regulatory protein gene in 2p23 in obese French caucasians. Diabetologia. 2003 May 9;46(5):704–711. doi: 10.1007/s00125-003-1083-y. [DOI] [PubMed] [Google Scholar]
  16. Veiga-da-Cunha M., Xu L. Z., Lee Y. H., Marotta D., Pilkis S. J., Van Schaftingen E. Effect of mutations on the sensitivity of human beta-cell glucokinase to liver regulatory protein. Diabetologia. 1996 Oct;39(10):1173–1179. doi: 10.1007/BF02658503. [DOI] [PubMed] [Google Scholar]
  17. Veiga-da-Cunha Maria, Van Schaftingen Emile. Identification of fructose 6-phosphate- and fructose 1-phosphate-binding residues in the regulatory protein of glucokinase. J Biol Chem. 2001 Dec 27;277(10):8466–8473. doi: 10.1074/jbc.M105984200. [DOI] [PubMed] [Google Scholar]
  18. Warner J. P., Leek J. P., Intody S., Markham A. F., Bonthron D. T. Human glucokinase regulatory protein (GCKR): cDNA and genomic cloning, complete primary structure, and chromosomal localization. Mamm Genome. 1995 Aug;6(8):532–536. doi: 10.1007/BF00356171. [DOI] [PubMed] [Google Scholar]

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