HPA axis dysfunction in STZ-diabetic rats: effects of lipoic acid and alpha-tocopherol treatment

ARIAS P; REPETTO EM; BONELLI AL; SANCHEZ R; MERCAU ME; CYMERYNG CB

Vienna

Congreso; 2014 Annual EASD Meeting; 2014

European Association for the Study of Diabetes

Background and aims: Glucocorticoid release is involved in glucose counterregulation, and a diminished or absent adrenocortical function renders non-diabetic as well as insulin-treated diabetic subjects prone to hypoglycemia. We previously demonstrated that STZ-diabetic rats show increased basal, but markedly reduced ACTH-stimulated corticosterone (CS) levels. Present experiments, performed in STZ-diabetic rats receiving lipoic acid (LA) or α-tocopherol (aT) treatment, were designed 1) to evaluate the effect of these treatments on oxidative stress parameters, on nitric oxide synthase (NOS) activity, and on steroidogenic function of the adrenal cortex of STZ-treated rats, and 2) to test the hypothesis that STZ-induced oxidative stress might modify CS release by affecting pituitary ACTH secretion. Materials and methods: Male Wistar rats (220-240g) were randomly assigned to the following groups: CON (control), STZ (2 injections of 40 mg/kg STZ separated by 48 h), LA (90 mg/kg ip every 48 h), aT (200 mg/kg/d po), STZ-LA or STZ-aT. LA, aT or vehicle were initiated immediately after the confirmation of hyperglycemia. After 4 weeks, all animals were sacrificed. Oxidative stress parameters and NOS activity, as well as the expression levels of CYP11A1, a key steroidogenic enzyme, and of the ACTH receptor MC2R were evaluated by RT-qPCR in the adrenal cortex. Plasma ACTH and serum CS levels (basal and ACTH-stimulated) were measured by RIA. After normality testing a one-way ANOVA was used for statistical evaluation. Results: STZ rats displayed elevated basal CS levels, and a diminished CS response to ACTH injection. Antioxidants decreased CS levels to those observed in controls (CON: 7.3 ± 2.5*, STZ: 71.7 ± 9.2, STZ aT: 5.8 ± 3.4*, STZ-LA: 19.1 ± 5.5* ng/ml; *p