Efeitos adversos da deficiência de vitamina D em ilhotas pancreáticas de camundongos alimentados com dieta hiperlipídica

Abstract

To evaluate the effects of vitamin D deficiency on body mass, hormonal profile, endocrine pancreas function and carbohydrate metabolism in animals that received high-fat diet with vitamin D restriction. Methods: C57BL/6 male mice were fed a control diet (SC) containing 10% energy from fat or a high-fat diet (HF) containing 50% energy from fat, with or without vitamin D for 8 weeks. Metabolic parameters, such as body mass and energy intake were analized; hormonal analyses of insulin, glucagon, leptin, adiponectin and 25(OH)D3 were performed as well as insulin and glucagon immunostaining; and molecular analyses such as protein expression in the Pi3k/Akt pathway were done. Results: The results showed that there were no differences in body mass between the HF and the HF/VitD- groups. Vitamin D deficiency in diet-induced obese mice exacerbated hyperinsulinemia (P=0.04), hyperleptinemia (P=0.0002), insulin resistance (HOMA-IR, P=0.04), and promoted changes in pancreatic islet function, including disarrangement of alpha cells and beta cells distribution. In the insulin signaling pathway, IRS2 expression was up-regulated in the SC/VitD- group (P=0.001) and down-regulated in the HF/VitD- group (P=0.009). Interestingly, FOXO1 expression was higher in the HF/VitD- group than the HF group (P=0.03) and the PDX1 expression was lower in the HF/VitD- group than the HF group (P=0.025), indicating that both the HF diet and the vitamin D deficiency influenced the regulation of these proteins expressions (two-way ANOVA, P<0.0001). Conclusions: Vitamin D deficiency exacerbates structural and physiological adverse remodeling of the pancreatic islet in obese mice, contributing to abnormal glucose homeostasis. These results suggest that this condition could anticipate type 2 diabetes mellitus onset in obese individuals.