| Summary: | 碩士 === 國立體育大學 === 運動保健學系碩士班 === 100 === Insulin resistance is a risk factor of several chronic metabolic diseases. In the previous studies, Acute Caffeine treatment decreased insulin sensitivity and insulin-stimulated glucose uptake in skeletal muscle; however, the precise mechanism responsible for this deleterious effect is not fully understood. In the present study, we investigated the effects and regulatory mechanism of caffeine on insulin sensitivity and glucose uptake in skeletal muscle cell. Differentiated C2C12 myotubes were treated with various times (0, 15, 30, 60 and 120 min) and concentrations (0, 1, 3 and 5 mM) of caffeine. After insulin (10-7 M) treatment for 10 min, phosphorylation of IRβ and Akt was analyzed using western blotting. Moreover insulin-induced glucose uptake was observed after caffeine (3 mM, 120 min) by in vitro glucose uptake assay. A Ca2+ release blocker, dantrolene (0.1 mM), was used to investigate the role of caffeine on insulin signaling pathway. Results showed that caffeine suppressed insulin-stimulated IRβ phosphorylation, Akt phosphorylation, and glucose uptake. On the other hand, caffeine increased intracellular Ca2+ level. Inhibition of Ca2+ release by sarcoplasmic reticulum using dantrolene did not rescue the caffeine-induced downregulation of IRβ and Akt phosphorylation. Furthermore, a NF-κB inhibitor curcumin, did not rescue the caffeine-induced downregulation of Akt phosphorylation. In conclusion, the inhibitory effects of caffeine on insulin-stimulated signaling and glucose uptake are mediated by Ca2+- and NF-κB-independent pathway.
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