The FASEB Journal, Vol 8, 414-419, Copyright © 1994 by The Federation of American Societies for Experimental Biology

REVIEWS

Short-term control of glucokinase activity: role of a regulatory protein

E Van Schaftingen, M Detheux and M Veiga da Cunha
Laboratoire de Chimie Physiologique, Universite Catholique de Louvain, Brussels, Belgium.

Glucokinase is one of the four hexokinases present in mammalian tissues. It is expressed in two cell types that have to respond to changes in the blood glucose concentration, the liver parenchymal cell and the beta-cells of pancreatic islets. The former are responsible for the metabolism and storage of an important part of the ingested glucose, whereas the latter secrete insulin in response to an increase in the blood glucose level. One major characteristic of glucokinase is that it has a relatively low affinity for glucose and displays positive cooperativity for this substrate, despite the fact that it is a monomeric enzyme. Furthermore, unlike other hexokinases, it is not inhibited by micromolar (physiological) concentrations of glucose 6- phosphate but by a regulatory protein that transduces the effect of fructose 6-phosphate and of fructose 1-phosphate. The purpose of this review is to describe these aspects of the regulation of glucokinase.

This article has been cited by other articles:

				M. Vaxillaire, C. Cavalcanti-Proenca, A. Dechaume, J. Tichet, M. Marre, B. Balkau, P. Froguel, and for the DESIR Study Group The Common P446L Polymorphism in GCKR Inversely Modulates Fasting Glucose and Triglyceride Levels and Reduces Type 2 Diabetes Risk in the DESIR Prospective General French Population Diabetes, August 1, 2008; 57(8): 2253 - 2257. [Abstract] [Full Text] [PDF]

				N. Bouatia-Naji, G. Rocheleau, L. Van Lommel, K. Lemaire, F. Schuit, C. Cavalcanti-Proenca, M. Marchand, A.-L. Hartikainen, U. Sovio, F. De Graeve, et al. A Polymorphism Within the G6PC2 Gene Is Associated with Fasting Plasma Glucose Levels Science, May 23, 2008; 320(5879): 1085 - 1088. [Abstract] [Full Text] [PDF]

				M. H. Mukhtar, V. A. Payne, C. Arden, A. Harbottle, S. Khan, A. J. Lange, and L. Agius Inhibition of glucokinase translocation by AMP-activated protein kinase is associated with phosphorylation of both GKRP and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R766 - R774. [Abstract] [Full Text] [PDF]

				V. A. Payne, C. Arden, A. J. Lange, and L. Agius Contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 to the elevated glycolysis in hepatocytes from Zucker fa/fa rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R618 - R625. [Abstract] [Full Text] [PDF]

				C. Arden, A. Trainer, N. de la Iglesia, K. T. Scougall, A. L. Gloyn, A. J. Lange, J. A.M. Shaw, F. M. Matschinsky, and L. Agius Cell Biology Assessment of Glucokinase Mutations V62M and G72R in Pancreatic {beta}-Cells: Evidence for Cellular Instability of Catalytic Activity Diabetes, July 1, 2007; 56(7): 1773 - 1782. [Abstract] [Full Text] [PDF]

				M. Futamura, H. Hosaka, A. Kadotani, H. Shimazaki, K. Sasaki, S. Ohyama, T. Nishimura, J.-i. Eiki, and Y. Nagata An Allosteric Activator of Glucokinase Impairs the Interaction of Glucokinase and Glucokinase Regulatory Protein and Regulates Glucose Metabolism J. Biol. Chem., December 8, 2006; 281(49): 37668 - 37674. [Abstract] [Full Text] [PDF]

				S. Baltrusch and M. Tiedge Glucokinase Regulatory Network in Pancreatic {beta}-Cells and Liver Diabetes, December 1, 2006; 55(Supplement_2): S55 - S64. [Abstract] [Full Text] [PDF]

				J. V. Sagen, S. Odili, L. Bjorkhaug, D. Zelent, C. Buettger, J. Kwagh, C. Stanley, K. Dahl-Jorgensen, C. de Beaufort, G. I. Bell, et al. From Clinicogenetic Studies of Maturity-Onset Diabetes of the Young to Unraveling Complex Mechanisms of Glucokinase Regulation Diabetes, June 1, 2006; 55(6): 1713 - 1722. [Abstract] [Full Text] [PDF]

				V. A. Payne, C. Arden, C. Wu, A. J. Lange, and L. Agius Dual Role of Phosphofructokinase-2/Fructose Bisphosphatase-2 in Regulating the Compartmentation and Expression of Glucokinase in Hepatocytes Diabetes, July 1, 2005; 54(7): 1949 - 1957. [Abstract] [Full Text] [PDF]

				M. Shiota, P. Galassetti, K. Igawa, D. W. Neal, and A. D. Cherrington Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1160 - E1167. [Abstract] [Full Text] [PDF]

				A. L. Gloyn, S. Odili, D. Zelent, C. Buettger, H. A. J. Castleden, A. M. Steele, A. Stride, C. Shiota, M. A. Magnuson, R. Lorini, et al. Insights into the Structure and Regulation of Glucokinase from a Novel Mutation (V62M), Which Causes Maturity-onset Diabetes of the Young J. Biol. Chem., April 8, 2005; 280(14): 14105 - 14113. [Abstract] [Full Text] [PDF]

				L. J. Hampson and L. Agius Increased Potency and Efficacy of Combined Phosphorylase Inactivation and Glucokinase Activation in Control of Hepatocyte Glycogen Metabolism Diabetes, March 1, 2005; 54(3): 617 - 623. [Abstract] [Full Text] [PDF]

				C. Arden, A. Harbottle, S. Baltrusch, M. Tiedge, and L. Agius Glucokinase Is an Integral Component of the Insulin Granules in Glucose-Responsive Insulin Secretory Cells and Does Not Translocate During Glucose Stimulation Diabetes, September 1, 2004; 53(9): 2346 - 2352. [Abstract] [Full Text] [PDF]

				Y. Fujimoto, E. P. Donahue, and M. Shiota Defect in glucokinase translocation in Zucker diabetic fatty rats Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E414 - E423. [Abstract] [Full Text] [PDF]

				S.-Y. Kim, H.-i. Kim, T.-H. Kim, S.-S. Im, S.-K. Park, I.-K. Lee, K.-S. Kim, and Y.-H. Ahn SREBP-1c Mediates the Insulin-dependent Hepatic Glucokinase Expression J. Biol. Chem., July 16, 2004; 279(29): 30823 - 30829. [Abstract] [Full Text] [PDF]

				J. J. Collier and D. K. Scott Sweet Changes: Glucose Homeostasis Can Be Altered by Manipulating Genes Controlling Hepatic Glucose Metabolism Mol. Endocrinol., May 1, 2004; 18(5): 1051 - 1063. [Abstract] [Full Text] [PDF]

				L. Massa, S. Baltrusch, D. A. Okar, A. J. Lange, S. Lenzen, and M. Tiedge Interaction of 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase (PFK-2/FBPase-2) With Glucokinase Activates Glucose Phosphorylation and Glucose Metabolism in Insulin-Producing Cells Diabetes, April 1, 2004; 53(4): 1020 - 1029. [Abstract] [Full Text] [PDF]

				C. A. Chu, Y. Fujimoto, K. Igawa, J. Grimsby, J. F. Grippo, M. A. Magnuson, A. D. Cherrington, and M. Shiota Rapid translocation of hepatic glucokinase in response to intraduodenal glucose infusion and changes in plasma glucose and insulin in conscious rats Am J Physiol Gastrointest Liver Physiol, April 1, 2004; 286(4): G627 - G634. [Abstract] [Full Text] [PDF]

				K. J. Brocklehurst, V. A. Payne, R. A. Davies, D. Carroll, H. L. Vertigan, H. J. Wightman, S. Aiston, I. D. Waddell, B. Leighton, M. P. Coghlan, et al. Stimulation of Hepatocyte Glucose Metabolism by Novel Small Molecule Glucokinase Activators Diabetes, March 1, 2004; 53(3): 535 - 541. [Abstract] [Full Text] [PDF]

				S.-y. Kim, H.-i. Kim, S.-K. Park, S.-S. Im, T. Li, H. G. Cheon, and Y.-h. Ahn Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-{gamma} Diabetes, February 1, 2004; 53(90001): S66 - 70. [Abstract] [Full Text]

				P. M. Heacock, S. R. Hertzler, and B. W. Wolf Fructose Prefeeding Reduces the Glycemic Response to a High-Glycemic Index, Starchy Food in Humans J. Nutr., September 1, 2002; 132(9): 2601 - 2604. [Abstract] [Full Text] [PDF]

				S. R. Commerford, J. B. Ferniza, M. E. Bizeau, J. S. Thresher, W. T. Willis, and M. J. Pagliassotti Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E545 - E555. [Abstract] [Full Text] [PDF]

				B. W. Wolf, P. M. Humphrey, C. W. Hadley, K. S. Maharry, K. A. Garleb, and J. L. Firkins Supplemental Fructose Attenuates Postprandial Glycemia in Zucker Fatty fa/fa Rats J. Nutr., June 1, 2002; 132(6): 1219 - 1223. [Abstract] [Full Text] [PDF]

				F. Rolland, B. Moore, and J. Sheen Sugar Sensing and Signaling in Plants PLANT CELL, May 1, 2002; 14(90001): S185 - 205. [Full Text] [PDF]

				M. Veiga-da-Cunha and E. Van Schaftingen Identification of Fructose 6-Phosphate- and Fructose 1-Phosphate-binding Residues in the Regulatory Protein of Glucokinase J. Biol. Chem., March 1, 2002; 277(10): 8466 - 8473. [Abstract] [Full Text] [PDF]

				M. Shiota, M. C. Moore, P. Galassetti, M. Monohan, D. W. Neal, G. I. Shulman, and A. D. Cherrington Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog Diabetes, February 1, 2002; 51(2): 469 - 478. [Abstract] [Full Text] [PDF]

				S. Baltrusch, S. Lenzen, D. A. Okar, A. J. Lange, and M. Tiedge 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 J. Biol. Chem., November 16, 2001; 276(47): 43915 - 43923. [Abstract] [Full Text] [PDF]

				K. F. Petersen, D. Laurent, C. Yu, G. W. Cline, and G. I. Shulman Stimulating Effects of Low-Dose Fructose on Insulin-Stimulated Hepatic Glycogen Synthesis in Humans Diabetes, June 1, 2001; 50(6): 1263 - 1268. [Abstract] [Full Text]

				N. de la Iglesia, M. Mukhtar, J. Seoane, J. J. Guinovart, and L. Agius The Role of the Regulatory Protein of Glucokinase in the Glucose Sensory Mechanism of the Hepatocyte J. Biol. Chem., March 31, 2000; 275(14): 10597 - 10603. [Abstract] [Full Text] [PDF]

				J. Grimsby, J. W. Coffey, M. T. Dvorozniak, J. Magram, G. Li, F. M. Matschinsky, C. Shiota, S. Kaur, M. A. Magnuson, and J. F. Grippo Characterization of Glucokinase Regulatory Protein-deficient Mice J. Biol. Chem., March 10, 2000; 275(11): 7826 - 7831. [Abstract] [Full Text] [PDF]

				F. Rencurel, M. J. Munoz-Alonso, J. Girard, and A. Leturque An Unusual High-Km Hexokinase Is Expressed in the mhAT3F Hepatoma Cell Line J. Biol. Chem., October 2, 1998; 273(40): 26187 - 26193. [Abstract] [Full Text] [PDF]

				R. M. O'Doherty, D. L. Lehman, J. Seoane, A. M. Gomez-Foix, J. J. Guinovart, and C. B. Newgard Differential Metabolic Effects of Adenovirus-mediated Glucokinase and Hexokinase I Overexpression in Rat Primary Hepatocytes J. Biol. Chem., August 23, 1996; 271(34): 20524 - 20530. [Abstract] [Full Text] [PDF]

				M. Veiga-da-Cunha, S. Courtois, A. Michel, E. Gosselain, and E. Van Schaftingen Amino Acid Conservation in Animal Glucokinases J. Biol. Chem., March 15, 1996; 271(11): 6292 - 6297. [Abstract] [Full Text] [PDF]

				T. C. Becker, R. J. Noel, J. H. Johnson, R. M. Lynch, H. Hirose, Y. Tokuyama, G. I. Bell, and C. B. Newgard Differential Effects of Overexpressed Glucokinase and Hexokinase I in Isolated Islets J. Biol. Chem., January 5, 1996; 271(1): 390 - 394. [Abstract] [Full Text] [PDF]

				A. Shiraishi, Y. Yamada, Y. Tsuura, S. Fijimoto, K. Tsukiyama, E. Mukai, Y. Toyoda, I. Miwa, and Y. Seino A Novel Glucokinase Regulator in Pancreatic beta Cells. PRECURSOR OF PROPIONYL-CoA CARBOXYLASE beta SUBUNIT INTERACTS WITH GLUCOKINASE AND AUGMENTS ITS ACTIVITY J. Biol. Chem., January 19, 2001; 276(4): 2325 - 2328. [Abstract] [Full Text] [PDF]

				M. J. Munoz-Alonso, G. Guillemain, N. Kassis, J. Girard, A.-F. Burnol, and A. Leturque A Novel Cytosolic Dual Specificity Phosphatase, Interacting with Glucokinase, Increases Glucose Phosphorylation Rate J. Biol. Chem., October 13, 2000; 275(42): 32406 - 32412. [Abstract] [Full Text] [PDF]

				J. An, Y. Li, G. van de Werve, and C. B. Newgard Overexpression of the P46 (T1) Translocase Component of the Glucose-6-phosphatase Complex in Hepatocytes Impairs Glycogen Accumulation via Hydrolysis of Glucose 1-Phosphate J. Biol. Chem., March 30, 2001; 276(14): 10722 - 10729. [Abstract] [Full Text] [PDF]