CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MODERATE EXERCISE PREVENTS MORPHOLOGICAL AND FUNCTIONAL ADRENOCORTICAL ALTERATIONS IN RATS WITH SUCROSE-INDUCED INSULIN RESISTANCE
Autor/es:
MARTINEZ CALJEMAN, CAMILA; DI GRUCCIO, JUAN MARTÍN; JAUME, DAIANA; SANCHEZ, ROCÍO; MERCAU, MARÍA ELISA; ASTORT, FRANCISCO; ARIAS, PABLO; CYMERYNG, CORA BEATRIZ
Lugar:
BERLIN
Reunión:
Congreso; 48th EASD Annual Meeting; 2012
Institución organizadora:
EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES
Resumen:
Background and aims: Previous results from our group demonstrate the impact of sucrose-induced insulin resistance on rat adrenocortical function and morphology. Physical activity reduces insulin resistance both in patients and in animal models with this metabolic derangement. Thus, we studied the effects of moderate physical exercise on the adrenocortical alterations already detected in rats with insulin resistance induced by sucrose-rich diets (SRD).Materials and methods: Adult male Wistar rats received 30% sucrose in the drinking water or their usual diet for a period of 9 weeks. Sucrose-treated and control animals underwent a protocol of moderate physical exercise on a treadmill (at 0.8 km/h up to 6 min, 5 days per week, groups SRD-E and C-E respectively). After 9 weeks, we measured insulin sensitivity (insulin tolerance test or ITT with 0.75 IU/kg insulin i.p.), adrenal function (basal and ACTH-stimulated serum corticosterone levels) and plasma ACTH levels. In adrenocortical tissue we determined triacylglyceride (TAG) and total cholesterol concentrations, the expression of proteins involved in steroidogenesis (StAR and CYP11A1) and its regulation (MCR2 ACTH receptor),  and inflammatory markers (TNF alpha, F4/80, COX-2).We also performed a histochemical evaluation of the adrenal cortex. Similar analysis were performed also in sedentary animals receiving a SRD (SRD-S) or their usual diet (C-S). Values are expressed as mean ± SEM. Differences between groups were analyzed by unpaired t test or by factorial one-way ANOVA followed by Tukey’s test, as appropriated. SRD-E animals exhibited lower body weight and glucose and insulin levels as compared to those measured in the corresponding SRD-S group.  Results obtained by means of the ITT showed a significant amelioration of the k value (SRD-E 1.88 ± 0.43 vs. SRD-S 1.68 ± 0.4,  mg*ml/min, p < 0.005). Insulin resistant animals submitted to the exercise protocol showed significantly lower levels of adrenal triacylglycerides (SRD-E 2.11 ± 0.17 vs. SRD-S 2.89 ± 0.19 µg*mg tissue, p<0.01). In agreement, the densitometric analysis of Sudan III staining of adrenocortical sections showed a significant decrease in lipid infiltration in SRD-E animals. Physical exercise also resulted in a significant decrease in the expression levels of CYP11A1, StAR, COX-2, F4/80 and TNF alpha, and in elevated MC2R mRNA levels, as compared to the results obtained in the SRD-S group. Finally, physical exercise blocked the increase in both basal ACTH (SRD-E 48.7 ± 5.56 vs. SRD 80.7 ± 7.57 pg/ml p< 0.05) and corticosterone (SRD-E 7.8 ± 0.11 vs. SRD 30.0 ± 0.10 ng/ml p< 0.005) levels present in SRD-S rats, and restored the subnormal adrenal response to acute ACTH stimulation (SRD-E 4890 ± 180 vs. SRD 3840 ± 131 AUC arbitrary units p< 0.005). Conclusion: The implementation of a moderate physical exercise protocol in SRD-treated animals normalized insulin sensitivity and prevented the onset of morphological and biochemical alterations in the adrenal cortex. This protocol also improved adrenal function and restored  the response to acute ACTH stimulation.  Taking these results, as well as previous data obtained using an insulin-sensitizing drug (rosiglitazone), in consideration,  a causal relationship between insulin resistance, increased adrenocortical lipid deposition and  deranged secretory function could be hypothesized.