FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ferre, T.
Right arrow Articles by Valera, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ferre, T.
Right arrow Articles by Valera, A.

The FASEB Journal, Vol 10, 1213-1218, Copyright © 1996 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Evidence from transgenic mice that glucokinase is rate limiting for glucose utilization in the liver

T Ferre, E Riu, F Bosch and A Valera
Departament de Bioquimica i Biologia Molecular, Facultat de Veterinaria, Universitat Autonoma de Barcelona, Bellaterra, Spain.

To study the role of glucokinase (GK) in the control of glucose metabolism in the liver, transgenic mice were generated in which GK was overexpressed under control of the P-enolpyruvate carboxykinase gene promoter. Whereas the expression of the GK gene in starved control mice was blocked, this promoter was able to direct the expression of the enzyme to the liver of starved transgenic mice. Furthermore, starved transgenic mice showed levels of GK activity fourfold higher than those of starved control and similar to those of fed control. This activation of GK led to an increase in the intracellular concentration of glucose 6-phosphate, which was also related to an induction of glycogen accumulation. In addition, L-pyruvate kinase (L-PK) activity increased in transgenic mice, which when starved showed similar levels of activity to control fed mice. The induction of L-PK caused an increase in the hepatic lactate concentration. Furthermore, hepatocytes in primary culture from transgenic mice incubated with 20 mM glucose produced levels of lactate threefold higher than controls, but no difference was noted when the hepatocytes from control and transgenic mice were incubated with 2 mM glucose. These results demonstrated in vivo that the activation of GK is a rate-limiting step in the induction of glycolysis and glycogen synthesis. These changes in liver glucose metabolism led to a marked reduction in blood glucose (30%) and insulin (40%) concentrations. Furthermore, transgenic mice showed lower levels of blood glucose after an intraperitoneal glucose tolerance test, indicating that GK overexpression caused an increase in blood glucose disposal by the liver. All these findings show the key role of liver GK in the control of whole-body glucose homeostasis.-Ferre, T., Riu, E., Bosch, F., Valera, A. Evidence from transgenic mice that glucokinase is rate limiting for glucose utilization in the liver.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. Petrak, D. Myslivcova, P. Man, R. Cmejla, J. Cmejlova, D. Vyoral, M. Elleder, and C. D. Vulpe
Proteomic analysis of hepatic iron overload in mice suggests dysregulation of urea cycle, impairment of fatty acid oxidation, and changes in the methylation cycle
Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1490 - G1498.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
Diabetes Genetics Initiative of Broad Institute of, R. Saxena, B. F. Voight, V. Lyssenko, N. P. Burtt, P. I. W. de Bakker, H. Chen, J. J. Roix, S. Kathiresan, J. N. Hirschhorn, et al.
Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels
Science, June 1, 2007; 316(5829): 1331 - 1336.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. F. Pino, K.-A. Kim, K. D. Shelton, J. Lindner, S. Odili, C. Li, H. W. Collins, M. Shiota, F. M. Matschinsky, and M. A. Magnuson
Glucokinase Thermolability and Hepatic Regulatory Protein Binding Are Essential Factors for Predicting the Blood Glucose Phenotype of Missense Mutations
J. Biol. Chem., May 4, 2007; 282(18): 13906 - 13916.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Y. Okamoto, W. Ogawa, A. Nishizawa, H. Inoue, K. Teshigawara, S. Kinoshita, Y. Matsuki, E. Watanabe, R. Hiramatsu, H. Sakaue, et al.
Restoration of Glucokinase Expression in the Liver Normalizes Postprandial Glucose Disposal in Mice With Hepatic Deficiency of PDK1
Diabetes, April 1, 2007; 56(4): 1000 - 1009.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. M. Efanov, D. G. Barrett, M. B. Brenner, S. L. Briggs, A. Delaunois, J. D. Durbin, U. Giese, H. Guo, M. Radloff, G. S. Gil, et al.
A Novel Glucokinase Activator Modulates Pancreatic Islet and Hepatocyte Function
Endocrinology, September 1, 2005; 146(9): 3696 - 3701.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
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]

Home page
 J. Biol. Chem.Home page
R. Dentin, J.-P. Pegorier, F. Benhamed, F. Foufelle, P. Ferre, V. Fauveau, M. A. Magnuson, J. Girard, and C. Postic
Hepatic Glucokinase Is Required for the Synergistic Action of ChREBP and SREBP-1c on Glycolytic and Lipogenic Gene Expression
J. Biol. Chem., May 7, 2004; 279(19): 20314 - 20326.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 DiabetesHome page
H.-i. Kim and Y.-h. Ahn
Role of Peroxisome Proliferator-Activated Receptor-{gamma} in the Glucose-Sensing Apparatus of Liver and {beta}-Cells
Diabetes, February 1, 2004; 53(90001): S60 - 65.
[Abstract] [Full Text]

Home page
 DiabetesHome page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. Mesotten, J. V. Swinnen, F. Vanderhoydonc, P. J. Wouters, and G. Van den Berghe
Contribution of Circulating Lipids to the Improved Outcome of Critical Illness by Glycemic Control with Intensive Insulin Therapy
J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 219 - 226.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. M. Valverde, D. J. Burks, I. Fabregat, T. L. Fisher, J. Carretero, M. F. White, and M. Benito
Molecular Mechanisms of Insulin Resistance in IRS-2-Deficient Hepatocytes
Diabetes, September 1, 2003; 52(9): 2239 - 2248.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. A. Magnuson, P. She, and M. Shiota
Gene-altered Mice and Metabolic Flux Control
J. Biol. Chem., August 29, 2003; 278(35): 32485 - 32488.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. M. Donmoyer, D. B. Lacy, Y. Zhang, S.-S. Chen, and O. P. McGuinness
Impact of chronic fructose infusion on hepatic metabolism during TPN administration
Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1151 - E1158.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
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]

Home page
 DiabetesHome page
E. D. Slosberg, U. J. Desai, B. Fanelli, I. St. Denny, S. Connelly, M. Kaleko, B. R. Boettcher, and S. L. Caplan
Treatment of Type 2 Diabetes by Adenoviral-Mediated Overexpression of the Glucokinase Regulatory Protein
Diabetes, August 1, 2001; 50(8): 1813 - 1820.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Shiota, C. Postic, Y. Fujimoto, T. L. Jetton, K. Dixon, D. Pan, J. Grimsby, J. F. Grippo, M. A. Magnuson, and A. D. Cherrington
Glucokinase Gene Locus Transgenic Mice Are Resistant to the Development of Obesity-Induced Type 2 Diabetes
Diabetes, March 1, 2001; 50(3): 622 - 629.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. Panserat, F. Medale, C. Blin, J. Breque, C. Vachot, E. Plagnes-Juan, E. Gomes, R. Krishnamoorthy, and S. Kaushik
Hepatic glucokinase is induced by dietary carbohydrates in rainbow trout, gilthead seabream, and common carp
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1164 - R1170.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Shiota, J. Coffey, J. Grimsby, J. F. Grippo, and M. A. Magnuson
Nuclear Import of Hepatic Glucokinase Depends upon Glucokinase Regulatory Protein, whereas Export Is Due to a Nuclear Export Signal Sequence in Glucokinase
J. Biol. Chem., December 24, 1999; 274(52): 37125 - 37130.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. Cabrera-Valladares, M. S. German, F. M. Matschinsky, J. Wang, and C. Fernandez-Mejia
Effect of Retinoic Acid on Glucokinase Activity and Gene Expression and on Insulin Secretion in Primary Cultures of Pancreatic Islets
Endocrinology, July 1, 1999; 140(7): 3091 - 3096.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
C. Postic, M. Shiota, K. D. Niswender, T. L. Jetton, Y. Chen, J. M. Moates, K. D. Shelton, J. Lindner, A. D. Cherrington, and M. A. Magnuson
Dual Roles for Glucokinase in Glucose Homeostasis as Determined by Liver and Pancreatic beta  Cell-specific Gene Knock-outs Using Cre Recombinase
J. Biol. Chem., January 1, 1999; 274(1): 305 - 315.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. K. Scott, R. M. O'Doherty, J. M. Stafford, C. B. Newgard, and D. K. Granner
The Repression of Hormone-activated PEPCK Gene Expression by Glucose Is Insulin-independent but Requires Glucose Metabolism
J. Biol. Chem., September 11, 1998; 273(37): 24145 - 24151.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
L. Rossetti, W. Chen, M. Hu, M. Hawkins, N. Barzilai, and S. Efrat
Abnormal regulation of HGP by hyperglycemia in mice with a disrupted glucokinase allele
Am J Physiol Endocrinol Metab, October 1, 1997; 273(4): E743 - E750.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. D. Niswender, M. Shiota, C. Postic, A. D. Cherrington, and M. A. Magnuson
Effects of Increased Glucokinase Gene Copy Number on Glucose Homeostasis and Hepatic Glucose Metabolism
J. Biol. Chem., September 5, 1997; 272(36): 22570 - 22575.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1996 by The Federation of American Societies for Experimental Biology.