RESUMEN
Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle.
Asunto(s)
Proteínas Quinasas Activadas por AMP/fisiología , Eugenol/análogos & derivados , Glucosa/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/genética , Animales , Calcio/análisis , Calcio/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/antagonistas & inhibidores , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Eugenol/farmacología , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Ratones , Fibras Musculares Esqueléticas/química , Fosforilación/efectos de los fármacos , ARN Interferente Pequeño/genética , Ratas , Transfección , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Thromboembolism is one of the most critical complications of hypereosinophilic syndrome (HES). We report here a case of multi-organ infarctions related to HES. A 23-year-old woman was referred to our hospital with hemoptysis. Not only pulmonary, but also renal and splenic infarctions were detected on computed tomography images. Blood tests showed profound peripheral eosinophilia. She was diagnosed with HES with disseminated intravascular coagulation (DIC). We initiated infusion of corticosteroids, which effectively suppressed peripheral eosinophilia. However, consumptive coagulopathy did not improve and intracerebral hemorrhage related to thrombosis then developed. Addition of interferon-alpha resulted in the correction of the DIC associated with HES.
