Effect of diabetes on enzymes involved in rat hepatic corticosterone production

Background:  Numerous studies have explored the etiologic or permissive role of 11β‐hydroxysteroid dehydrogenase (11β‐HSD1) in obesity and Type 2 diabetes, biochemical conditions often with concurrent hyperinsulinism. In contrast, there are limited data on the effect of insulin deficiency (i.e. Type 1 diabetes) on 11β‐HSD1 or endoplasmic reticulum enzymes that generate the reduced pyridine cofactor NADPH. Thus, the aim of the present study was to examine the effect of insulin‐deficient, streptozotozin diabetes on key microsomal enzymes involved in rat hepatic corticosterone production. Methods:  After rats had been rendered diabetic with streptozotocin and some had been treated with insulin (2–6 units, s.c., long‐acting insulin once daily) for 7 days, hepatic microsomes were isolated. Serum corticosterone and fructosamine were obtained premortem. Intact microsomes were incubated in vitro and 11β‐HSD1, hexose‐6‐phosphate dehydrogenase (H6PDH), and isocitrate dehydrogenase (IDH) measured. Results:  Although diabetes markedly altered body weight gain and serum protein glycosylation (assessed by fructosamine), there was no significant change in hepatic 11β‐HSD1 reductase activity, with or without insulin treatment. However, serum corticosterone levels were significantly correlated with 11β‐HSD1 reductase activity when all groups were analyzed together ( P  < 0.05). Untreated diabetes modified ( P  < 0.01) two hepatic microsomal NADPH‐generating enzymes, namely H6PDH and IDH, resulting in a 37% decrease and 14% increase in enzyme levels, respectively. Conclusions:  Consistent with most in vivo studies, chronic insulin deficiency with attendant hyperglycemia does not significantly modify hepatic 11β‐HSD1 reductase activity, but does alter the activity of two microsomal enzymes coupled with pyridine cofactors.