Comparative effects of genetic obesity and streptozotocin-diabetes on rat liver cytosolic glutathione S-transferase activities

Abstract

The effect of genetic obesity and streptozotocin-induced diabetes on cytosolic glutathione S-transferase (GST) activity was investigated in male rat liver with a series of substrates that reflect the activity of individual GSTs. In diabetic rat liver the conjugations with glutathione of three GST substrates-1-chloro-2,4-dinitrobenzene (CDNB), -nitrobenzyl chloride (PNBC) and 1,2-dichloro-4-nitrobenzene (DCNB) — were decreased to 47–63% of control; incomplete reversal of this effect was produced by insulin supplementation. The conjugations of trans-4-phenyl-3-buten-2-one (TPBO) and 1,2-epoxy-3-(-nitrophenoxy)propane (ENPP) were unchanged from control rates. Studies conducted in hyperinsulinemic genetically-obese Zucker rats revealed similar, but not identical, changes in GST activities. Of major interest was the observation that TPBO conjugation was markedly decreased to 59% of lean control, whereas this activity was unchanged from control in diabetic liver. These findings suggest that non-uniform effects on GST substrate conjugation occur in experimental diabetes and in genetic obesity The decreased capacity of diabetic liver cytosol to catalyse the conjugation of DCNB and PNBC with glutathione, with no apparent impairment in GST activity toward ENPP and TPBO, is consistent with lowered levels of GST 3-3 However, lower TPBO conjugation in obese rat liver suggests that the cytosolic content of GSTs 3–4 and 4-4 is decreased in these animals. The present study establishes that the reversal of diabetes-related losses of GST activities by insulin is incomplete and is substrate-dependent.