Insulin sensitization with a peroxisome proliferator-activated receptor γ agonist prevents adrenocortical lipid infiltration and secretory changes induced by a high-sucrose diet.

It has been hypothesized that deviations in glucocorticoid secretion and/or action may contribute to somatic and biochemical changes observed in patients with and animal models of insulin resistance (IR). In this study, we analyzed changes in rat adrenocortical function and morphology associated with the development of IR, generated in male adult rats by the addition of 30% sucrose to the drinking water. Caloric intake, body and adipose tissue weights, and biochemical parameters associated with IR were determined.

Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation.

Stimulation of adrenal steroidogenesis is involved in the HPA response to exogenous noxa. Although inflammatory cytokines can mediate the LPS-triggered activation of the HPA, direct effects of LPS on glucocorticoid release have been described. Present studies were undertaken to characterize the molecular mechanisms underlying the effect of LPS on steroid secretion in isolated rodent adrenal cells, assessing the participation of NFκB and COX-2 activities in this response.

High glucose-induced changes in steroid production in adrenal cells.

Background: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in enhanced adrenocorticotropin (ACTH) and serum glucocorticoid levels, has been described in patients with diabetes mellitus and in animal models of this disease; however, altered steroid production by adrenocortical cells could result from local changes triggered by increased reactive oxygen species (ROS), induced in turn by chronic hyperglycaemia. Experiments were designed (1) to analyse the effects of incubating murine adrenocortical cells in hyperglycaemic media on the generation of oxidative stress, on steroid synthesis and on its modulation by the activity of haeme oxygenase (HO); and (2) to evaluate the effect of antioxidant treatment on these parameters.

Methods: Y1 cells were incubated for 7 days with either normal or high glucose (HG, 30 mmol/L) concentrations, with or without antioxidant treatment.