Background and hypotheses: Recent results showing elevated tetrahydrocortisol/tetrahydrocorticosterone ratio (THFs/THE) in morning urines of diabetic children compared to controls suggest an increased nocturnal activity of 11 β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). We made the hypothesis that a reduced inhibition of hepatic 11β-HSD1 activity by exogenous insulin, due to its subcutaneous (SC) administration and absence of first hepatic passage, could explain these observations.
Objective: Our main objective was to compare 11β-HSD1 activity and expression in the liver of young diabetic rats, treated either by subcutaneous (SC) or intraperitoneal (IP) insulin. Our hypothesis was that hepatic 11β-HSD1 is less inhibited by SC insulin than by IP insulin.
Method: We formed 4 groups of juvenile Wistar rats: 12 controls, 36 streptozotocin-induced diabetic rats among them 12 were not treated (NT), 12 were treated with SC insulin and 12 with IP insulin. We measured 11β-HSD1 expression and activity in the liver at 7 weeks of life.
Results: Hepatic gene expression and activity of 11β-HSD1 were increased in the untreated diabetic group compared to controls. Although diabetes was controlled equally whatever the route of insulin administration, 11β-HSD1 gene expression and activity were only decreased in the IP group.
Conclusion: Ours results support that hepatic first pass is needed for 11β-HSD1 hepatic inhibition.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology