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The third group, comprising Cyp1a2 and Cyp7b1 , showed a decrease in the level of mRNA in diabetic mice, coupled with a further (nonsignificant) decrease in hyperinsulinemic animals.

The expression of Cyp2b9 , Cyp2c29 , Cyp3a16 , and Cyp7b1 was sexually dimorphic. With the exception of Cyp7b1 , expression was lower in male mice compared with females. The dimorphism for Cyp2b9 could also be extended to the effect of physiological state, with the level of this transcript increased in hyperinsulinemic males yet unchanged in hyperinsulinemic females. Similarly, although the level of expression of the putative Cyp2c22 was the same in normoglycemic males and females, a decrease in Cyp2c22 mRNA levels was observed with hyperinsulinemia in male mice only. Diet also influenced the expression of Cyp1a2 , Cyp3a16 , and Cyp4a14 isoforms. Cyp4a14 mRNA levels were higher in both males and females receiving a fat-enriched diet. On the other hand, the levels of Cyp1a2 (males and females) and Cyp3a16 (males) mRNA were decreased by a fat-enriched diet compared with a standard diet (Fig. Robert Clergerie Suede Alice Mules gRkcomZ5AA
).

No differences in expression of Cyp2e1 were observed among all groups, although this isoform has been found to be induced in other models of diabetes ( Simple® Satire Sneaker Waq30hy
). Similarly, the level of Cyp2j5 was not affected by hyperinsulinemia, diabetes, sex, or diet.

The expression of both Gstm3 and Gstm6 mRNA in NSZO mice followed the third pattern of expression described in the previous section, with a reduction in mRNA levels for these two isoforms in diabetic animals. Hyperinsulinemia seemed to reduce this expression to an even greater extent (Fig. 3 ).

Figure 3

Analysis of expression in normoglycemic (N), diabetic (D), and hyperglycemic (H) NSZO mice fed on a fat-enriched or standard diet. Animals maintained on standard diet were of normal glucose status. Northern blots of pooled hepatic RNA from individuals from each group and bar diagrams from dot-blot analysis of individuals from each group are shown. Data expressed as a percentage relative to the male high-fat normoglycemic group (mean ± S.E.).

The level of expression of Gstt2 was low in all animal groups. However, the pattern of expression observed for this transcript did not conform with any of the three patterns identified above. This isoform was up-regulated in diabetic male animals and down-regulated with hyperinsulinemia for both male and females (Fig. 3 ).

No change in Gsta2 mRNA was detected with the onset of diabetes or hyperinsulinemia. No differences between males and females were found for all of the GST isoforms studied. A fat-enriched diet seemed to cause some down-regulation for Gsta2 (males only).

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