RESUMEN
There is a tendency for the incidence of diabetes in a population to increase with an improvement in living standards. This would imply the involvement of nutritional factors in the development of diabetes, and so nutritional considerations could be a key aspect in the research and development of an effective remedy for diabetes. In this study, combined micronutrients (selenium, vitamin E, vanadium, and chromium) were orally supplemented to streptozotocin-induced diabetic mice. Results showed that combined micronutrients could decrease the high blood glucose levels (p<0.05 or p<0.01) of diabetic mice. The protective effects of combined micronutrients on structures of beta-cells in pancreatic islets of diabetic mice were observed histopathologically and ultrastructurally. In addition, the supplementation of combined micronutrients increased insulin expression by beta-cells in pancreatic islets of diabetic mice at both translational and transcriptional levels. The immune molecular mechanisms involved were preliminarily regarded as downregulation of the expression of pathogenic T-helper 1 lymphocyte (Th1) cytokine tumor necrosis factor-alpha (TNF-alpha) (p<0.01) along with upregulation of the expression of protective T-helper 2 lymphocyte Th2 cytokine interleukin 10 (IL-10) (p<0.01) which ameliorates the Th1/Th2 imbalance in diabetes. In conclusion, supplementation of combined micronutrients to diabetic mice could effectively improve disordered glucose metabolism, protect islet structures, and improve the function of beta-cells in pancreatic islets, which are affected by differential regulation of the expression of Th1/Th2 cytokines involved in the pathogenesis of diabetes.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Suplementos Dietéticos , Células Secretoras de Insulina/ultraestructura , Micronutrientes , Sustancias Protectoras , Animales , Glucemia/análisis , Cromo , Citocinas/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Experimental/patología , Inmunohistoquímica , Hibridación in Situ , Insulina/genética , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Selenio , Linfocitos T Colaboradores-Inductores/metabolismo , Vanadio , Vitamina ERESUMEN
OBJECTIVE: To investigate the regulatory effects of micronutrients complex (MC) on the expression of Th1 and Th2 cytokines in diabetic mice for exploring the molecular mechanisms of MC in treating for diabetes. METHODS: IDDM mice model was made by the injection of multiple low dose of streptozotocin (MLDS). The composition of Selenium (Se), Vitamin E (VE), Vanadium (V) and Chrome (Cr) was supplemented. The percentage of Th1 cytokines(TNF-alpha, IFN-gamma) and Th2 cytokines (IL-4, IL-10) positive lymphocytes were detected by flow cytometer (FCM). RESULTS: The expression of TNF-alpha and IFN-gamma of peripheral blood lymphocytes of MLDS group significantly increased (P < 0.01), while the IL-10 expression of blood and spleen lymphocytes of MLDS group obviously decreased (P < 0.01). Combined supplementation of MC markedly decreased blood lymphocytes TNF-alpha expression (P < 0.01) and increased blood lymphocytes IL-10 expression (P < 0.01) and spleen lymphocytes IL-4 expression (P < 0.05) of IDDM mice respectively. CONCLUSION: MC may prevent from the onset and development of IDDM by down-regulating Th1 cytokines genes expression and up-regulating Th2 cytokines genes expression of IDDM mice.