HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shiota, M. Articles by Cherrington, A. D. Search for Related Content PubMed PubMed Citation Articles by Shiota, M. Articles by Cherrington, A. D. Social Bookmarking                What's this?

Glucokinase Gene Locus Transgenic Mice Are Resistant to the Development of Obesity-Induced Type 2 Diabetes

¹ Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt University, Nashville, Tennessee
² Department of Metabolic Disease, Hoffmann-La Roche Inc., Nutley, New Jersey

Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been previously shown to be mildly hypoglycemic and to have improved tolerance to glucose. To determine whether increased GK might also prevent or diminish diabetes in diet-induced obese animals, we examined the effect of feeding these mice a high-fat high–simple carbohydrate low-fiber diet (HF diet) for 30 weeks. In response to this diet, both normal and transgenic mice became obese and had similar BMIs (5.3 ± 0.1 and 5.0 ± 0.1 kg/m² in transgenic and nontransgenic mice, respectively). The blood glucose concentration of the control mice increased linearly with time and reached 17.0 ± 1.3 mmol/l at the 30th week. In contrast, the blood glucose of GK transgenic mice rose to only 9.7 ± 1.2 mmol/l at the 15th week, after which it returned to 7.6 ± 1.0 mmol/l by the 30th week. The plasma insulin concentration was also lower in the GK transgenic animals (232 ± 79 pmol/l) than in the controls (595 ± 77 pmol/l), but there was no difference in plasma glucagon concentrations. Together, these data indicate that increased GK levels dramatically lessen the development of both hyperglycemia and hyperinsulinemia associated with the feeding of an HF diet.

Abbreviations: ANOVA, analysis of variance; DTT, dithioerythritol; G6Pase, glucose-6-phosphatase; GK, glucokinase; GKRP, GK regulatory protein; HF diet, high-fat high–simple carbohydrate low-fiber diet; NEFA, nonesterified fatty acid

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				J.-S. Shin, T. P. Torres, R. L. Catlin, E. P. Donahue, and M. Shiota A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1381 - R1390. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				J. Grimsby, R. Sarabu, W. L. Corbett, N.-E. Haynes, F. T. Bizzarro, J. W. Coffey, K. R. Guertin, D. W. Hilliard, R. F. Kester, P. E. Mahaney, et al. Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy Science, July 18, 2003; 301(5631): 370 - 373. [Abstract] [Full Text] [PDF]

				M. Guerre-Millo, C. Rouault, P. Poulain, J. Andre, V. Poitout, J. M. Peters, F. J. Gonzalez, J.-C. Fruchart, G. Reach, and B. Staels PPAR-{alpha}-Null Mice Are Protected From High-Fat Diet-Induced Insulin Resistance Diabetes, December 1, 2001; 50(12): 2809 - 2814. [Abstract] [Full Text] [PDF]

				U. J. Desai, E. D. Slosberg, B. R. Boettcher, S. L. Caplan, B. Fanelli, Z. Stephan, V. J. Gunther, M. Kaleko, and S. Connelly Phenotypic Correction of Diabetic Mice by Adenovirus-Mediated Glucokinase Expression Diabetes, October 1, 2001; 50(10): 2287 - 2295. [Abstract] [Full Text]