Effect of diabetes on enzymes involved in rat hepatic corticosterone production

Academic Article

Abstract

  • 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. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.
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    Digital Object Identifier (doi)

    Author List

  • Hyatt T; Chen R; Wang X; Mick G; McCormick K
  • Start Page

  • 275
  • End Page

  • 281
  • Volume

  • 2
  • Issue

  • 4