congresos y reuniones científicas
Sucrose-induced insulin resistance is accompanied by morphologic and functional changes in the adrenal cortex of the rat
Estocolmo, Suecia
Congreso; 46th Meeting of the European Association for the Study of Diabetes (EASD); 2010
Institución organizadora:
European Association for the Study of Diabetes (EASD)
Background and aims: Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis has been widely described in both human and animals showing insulin resistance (IR). However, a direct effect of the biochemical abnormalities that characterize this syndrome (e.g. elevated plasma glucose, serum insulin and free fatty acid levels, hypertriglicerydemia and oxidative stress) on adrenal function has not been elucidated yet. In this study we assesed the effect of a sucrose-enriched diet (SED) on adrenocortical structure and function (corticosterone secretion) in rats. Materials and methods: Male Wistar rats were fed a sucrose-enriched diet (SED, drinking water contaning 30% w/v sucrose) up to 12 weeks. Rosiglitazone (4mg/kg, orally and daily) was administered throughout the duration of the sucrose treatment to a group of animals. Protein levels of different isoforms of nitric oxide synthase (NOS), phosphorylated Akt and cyclooxygenase 2 (COX-2) were analyzed by immunoblot while mRNA levels of steroidogenic acute regulatory protein (StAR) and the macrophage marker F4/80 were assesed by semiquantitative RT-PCR. Steroid levels were determined by RIA. Sudan III staining was performed on adrenocortical slices previously fixed in 4% formaldehyde. Results: As compared to controls, rats under SED for 7 weeks showed higher fasting plasma  glucose (74 ± 5 and 130 ± 6 mg/dl; p<0,001, Mann-Whitney test) and serum triacylglyceride (104 ± 52 vs.604 ± 60 mg/dl; p<0,001) and insulin concentrations (0.99 ± 0.14 vs. 1.97 ± 0.4 ng/ml; p<0,005). An impairment in the insulin signalling pathway was detected at adrenal level as decreased p-Akt protein levels were measured by immunoblot analysis. The adrenal glands were lighter and showed a significant lipidic infiltration, as demonstrated by histochemistry. NOS activity and the expression levels of eNOS, iNOS and COX-2 were increased in the SED group. StAR and F4/80 mRNAs were also elevated. These animals showed significantly elevated basal serum corticosterone levels (6,63 ± 1,14 vs. 9,62 ± 0,84 ng/ml p<0,001) but a lower response to an acute stimulation with 4 UI/kg ACTH i.v., (115,68 ± 34, 03 vs 40,59 ± 25,39 percentage stimulation, p<0,05). On another set of experiments, rosiglitazone, a selective PPARgamma agonist, reverted the nutritionally-induced changes in NOS activity and corticosterone levels and decreased lipid infiltration in the adrenal tissue. Conclusions: A sucrose enriched diet seems to induce IR at adrenal level after 7 weeks of treatment, generating morphological and functional disturbances that finally could lead to the dysregulation of adrenal steroidogenesis. In this sense, the increase in NOS activity could trigger posttranscriptional modifications of several proteins (nitration, S-nitrosilation etc). Among them, those involved in steroid biosynthesis and its regulation. Both COX-2 and F4/80 could also be related to the chronic inflammatory state linked to IR in several tissues. Finally, some of these effects were prevented by rosiglitazone treatment, suggesting a signal transduction pathway that could be a target for pharmacological interventions designed to ameliorate this adrenal disfunction.