Diabetes, Vol 42, Issue 12 1731-1736, Copyright © 1993 by American Diabetes Association

ARTICLES

Impaired regulation of hepatic fructose-1,6-bisphosphatase in the New Zealand obese mouse model of NIDDM

S Andrikopoulos, G Rosella, E Gaskin, A Thorburn, S Kaczmarczyk, JD Zajac and J Proietto
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.

The New Zealand obese mouse, a model of NIDDM, is characterized by hyperglycemia, hyperinsulinemia, and hepatic and peripheral insulin resistance. The aim of this study was to investigate the biochemical basis of hepatic insulin resistance in NZO mice. Glycolytic and gluconeogenic enzyme activities were measured in fed and overnight fasted 19- to 20-wk-old NZO and control New Zealand chocolate mice. The NZO mice were twice as heavy as the NZC mice. The activity of the glycolytic enzymes glucokinase and pyruvate kinase was higher, whereas that of the gluconeogenic enzymes PEPCK and glucose-6-phosphatase was lower in fed and fasted NZO mice. These enzyme changes are consistent with a normal response to the hyperinsulinemia in NZO mice. In contrast, the activity of the third regulated gluconeogenic enzyme, fructose-1,6-bisphosphatase, was similar in fed and fasted NZO and NZC mice despite the higher insulin and glucose levels in the NZO mouse. This enzyme is primarily regulated by the powerful inhibitor fructose-2,6-bisphosphate. The levels of this metabolite were measured and found to be increased in both the fed and fasted states in the NZO mouse, suggesting that the activity of the bifunctional enzyme that regulates the level of inhibitor (6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase) is normally regulated in the NZO mouse. We conclude that most insulin-responsive gluconeogenic and glycolytic enzymes are normally regulated in the NZO mouse, but an abnormality in the regulation of fructose-1,6-bisphosphatase may contribute to the increase hepatic glucose production in these mice.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Kebede, J. Favaloro, J. E. Gunton, D. R. Laybutt, M. Shaw, N. Wong, B. C. Fam, K. Aston-Mourney, C. Rantzau, A. Zulli, et al. Fructose-1,6-Bisphosphatase Overexpression in Pancreatic {beta}-Cells Results in Reduced Insulin Secretion: A New Mechanism for Fat-Induced Impairment of {beta}-Cell Function Diabetes, July 1, 2008; 57(7): 1887 - 1895. [Abstract] [Full Text] [PDF]

				B. J. Lamont, S. Visinoni, B. C. Fam, M. Kebede, B. Weinrich, S. Papapostolou, H. Massinet, J. Proietto, J. Favaloro, and S. Andrikopoulos Expression of Human Fructose-1,6-Bisphosphatase in the Liver of Transgenic Mice Results in Increased Glycerol Gluconeogenesis Endocrinology, June 1, 2006; 147(6): 2764 - 2772. [Abstract] [Full Text] [PDF]

				S. Kooptiwut, M. Kebede, S. Zraika, S. Visinoni, K. Aston-Mourney, J. Favaloro, C. Tikellis, M. C Thomas, J. M Forbes, M. E Cooper, et al. High glucose-induced impairment in insulin secretion is associated with reduction in islet glucokinase in a mouse model of susceptibility to islet dysfunction J. Mol. Endocrinol., August 1, 2005; 35(1): 39 - 48. [Abstract] [Full Text] [PDF]

				E. H. Leiter and P. C. Reifsnyder Differential Levels of Diabetogenic Stress in Two New Mouse Models of Obesity and Type 2 Diabetes Diabetes, February 1, 2004; 53(90001): S4 - 11. [Abstract] [Full Text]

				R. H. Lane, N. K. MacLennan, J. L. Hsu, S. M. Janke, and T. D. Pham Increased Hepatic Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1 Gene Expression in a Rat Model of Intrauterine Growth Retardation and Subsequent Insulin Resistance Endocrinology, July 1, 2002; 143(7): 2486 - 2490. [Abstract] [Full Text] [PDF]

				S. Kooptiwut, S. Zraika, A. W. Thorburn, M. E. Dunlop, R. Darwiche, T. W. Kay, J. Proietto, and S. Andrikopoulos Comparison of Insulin Secretory Function in Two Mouse Models with Different Susceptibility to {beta}-Cell Failure Endocrinology, June 1, 2002; 143(6): 2085 - 2092. [Abstract] [Full Text] [PDF]

				S. Song, S. Andrikopoulos, C. Filippis, A. W. Thorburn, D. Khan, and J. Proietto Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin Am J Physiol Endocrinol Metab, August 1, 2001; 281(2): E275 - E282. [Abstract] [Full Text] [PDF]