Diabetes and Insulin Injection Modalities: Effects on Hepatic and Hippocampal Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Juvenile Diabetic Male Rats.
Front. Endocrinol.. 2017-04-18; 8:
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Rougeon V(1), Moisan MP(2)(3), Barthe N(4), Beauvieux MC(5), Helbling JC(2)(3), Pallet V(2)(6), Marissal-Arvy N(2)(3), Barat P(1)(3).
(1)Unité d’endocrinologie et de diabétologie pédiatrique, CHU de Bordeaux, Hôpital des Enfants, Bordeaux, France.
(2)INRA, Laboratoire de Nutrition et Neurobiologie Intégrée, UMR 1286, Bordeaux, France.
(3)University of Bordeaux, Nutrition et neurobiologie intégrée, UMR 1286, Bordeaux, France.
(4)Laboratoire mixte de Biophysique – INSERM U1026 BioTis, Bordeaux, France.
(5)Laboratoire de Biochimie de l’Hôpital Haut-Lévêque, Pessac, France.
(6)Bordeaux INP, Talence, France.
BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is
often encountered in diabetes, leading to several clinical complications. Our
recent results showing an elevated tetrahydrocortisol/tetrahydrocorticosterone
ratio in morning urine of diabetic children compared to that of controls suggest
an increased nocturnal activity of 11β-hydroxysteroid dehydrogenase type 1
(11β-HSD1) in the former.
QUESTION: We hypothesized that these observations could be explained by a reduced
inhibition of hepatic 11β-HSD1 activity by exogenous insulin owing to its
subcutaneous (SC) administration and absence of first hepatic passage.
Additionally, we hypothesized that hippocampal 11β-HSD1 activity might also be
impaired by diabetes.
METHODS: We therefore measured HPA axis activity and 11β-HSD1 expression and
activity in liver and hippocampus in streptozotocin-induced diabetic juvenile
rats treated with SC or intraperitoneal (IP) insulin.
RESULTS: Plasma corticosterone levels were elevated in untreated diabetic rats
during the resting phase and restored by both types of insulin treatment. The
mRNA expression and activity of 11β-HSD1 were increased in the untreated diabetic
group in liver. Although diabetes was controlled equally whatever the route of
insulin administration, liver 11β-HSD1 gene expression and activity was decreased
only in the IP group, suggesting that a first hepatic pass is needed for 11β-HSD1
hepatic inhibition. In hippocampus, 11β-HSD1 activity was elevated in the
untreated diabetic group but restored by both types of insulin treatment. Thus,
these data extend our findings in diabetic children by showing impairment of
hippocampal 11β-HSD1 in diabetes and by demonstrating that IP is preferable to SC
insulin administration to restore 11β-HSD1 activity in liver.