Elsevier

Metabolism

Volume 45, Issue 5, May 1996, Pages 622-626
Metabolism

Impaired regulation of hepatic fructose-1,6-bisphosphatase in the New Zealand obese mouse: An acquired defect

https://doi.org/10.1016/S0026-0495(96)90034-7Get rights and content

Abstract

Increased hepatic glucose production, a feature of (non—insulin-dependent diabetes mellitus [NIDDM] is present at an early age in the New Zealand Obese (NZO) mouse and is associated with impaired suppression of the gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase). The aim of this study was to further characterize the abnormality in the regulation of hepatic FBPase in NZO mice versus New Zealand Chocolate (NZC) control mice. At 20 weeks of age, NZO mice have elevated FBPase activity (65.3 ± 7.9 v 46.7 ± 5.0 μmol/min/mg protein, P = .07) and protein levels (31.7 ± 3.1 v 22.5 ± 2.8 arbitrary units, P < .05), but not mRNA levels (0.18 ± 0.03 v 0.16 ± 0.03 arbitrary units). Elevated FBPase activity and protein levels in NZO mice were also shown at 4 to 6 weeks of age, but not in 1-day-old mice, suggesting that the increase occurs between birth and weaning. The Km of the enzyme was the same in NZO and NZC mice (3.7 ± 0.5 v 5.0 ± 0.9 μmol/L, NZO v NZC). The regulation of FBPase by the competitive inhibitor, fructose-2,6-bisphosphate ([Fru(2,6)Pz] 5 μmol/L) measured over a range of substrate concentrations (2.5 to 80 μmol/L) was similar between NZO and control mice (Km in the presence of Fru(2,6)Pz, 10.8 ± 1.9 v 13.2 ± 3.3 μmol/L, NZO v NZC). It is concluded that increased FBPase activity in the NZO mouse is due to elevated protein levels, and that this appears to be due to a failure of the normal decrease that occurs following birth in control animals.

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    Supported by a program grant from the National Health and Research Council of Australia and by a grant-in-aid from Apex/ Diabetes Australia Research and Education.

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