RESUMO
Red pepper seed, a by-product of red pepper, has been reported to have antioxidant and antiobesity activities. However, its role in diabetes has not yet been highly investigated. Glucose homeostasis is mainly maintained by insulin, which suppresses glucose production in the liver and enhances glucose uptake in peripheral tissues. In this study, we investigated the underlying mechanisms through which red pepper seed extract (RPSE) affects glucose production in AML12 hepatocytes and glucose uptake in C2C12 myotubes. RPSE reduced glucose production in a dose-dependent manner in AML12 cells. The levels of glucose 6 phosphatase, phosphoenolpyruvate carboxykinase, and critical enzymes for hepatic gluconeogenesis were decreased by RPSE. Gluconeogenesis regulating proteins, Akt and forkhead box protein O1, were also activated by RPSE. In addition, RPSE increased glucose uptake in C2C12 via inducing translocation of glucose transporter type 4 from cytosol to plasma membrane. Analysis of the insulin-dependent pathway showed that the activities of insulin receptor substrate 1, phosphatidylinositol 3-kinase, and Akt were significantly stimulated by RPSE. In conclusion, RPSE might improve glucose homeostasis by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. Results obtained also suggest that RPSE can be a compelling antidiabetic nutraceutical.
Assuntos
Capsicum/química , Gluconeogênese/efeitos dos fármacos , Glucose/metabolismo , Fígado/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Glucose-6-Fosfatase/genética , Glucose-6-Fosfatase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sementes/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Korean red pine (Pinus densiflora) bark extract, PineXol (PX), was investigated for its potential antioxidant and anti-inflammation effects in vitro. It was hypothesized that PX treatment (25-150 µg/ml) would reduce the lipid synthesis in HepG2 hepatocytes as well as lipid accumulation in 3T3-L1 adipocytes. Hepatocytes' intracellular triglycerides and cholesterol were decreased in the PX 150 µg/ml treatment group compared with the control (p < 0.05). Consequently, de novo lipogenic proteins (acetyl-CoA carboxylase 1, stearoyl-CoA desaturase 1, elongase of very long chain fatty acids 6, glycerol-3-phosphate acyltransferase 1, and sterol regulatory element-binding protein 1) were significantly decreased in hepatocytes by PX 150 µg/ml treatment compared with the control (p < 0.05). In differentiated 3T3-L1 adipocytes, the lipid accumulation was significantly attenuated by all PX treatments (p < 0.01). Regulators of adipogenesis, including CCAAT-enhancer-binding proteins alpha, peroxisome proliferator-activated receptor gamma, and perilipin, were decreased in PX 100 µg/ml treatment compared with the control (p < 0.05). In conclusion, PX might have anti-obesity effects by blocking hepatic lipogenesis and by inhibiting adipogenesis in adipocytes.