腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)是一种广泛参与多种代谢调节的激酶,是主要的细胞"能量感受器"。AMPK通过α亚基的Thr172发生磷酸化而激活,通过抑制脂质合成相关转录因子以及肝脏糖异生来控制脂质合...腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)是一种广泛参与多种代谢调节的激酶,是主要的细胞"能量感受器"。AMPK通过α亚基的Thr172发生磷酸化而激活,通过抑制脂质合成相关转录因子以及肝脏糖异生来控制脂质合成以及血糖稳定。肝脏糖异生的调控过程中,通过激素及转录因子如Fox O1、CREB、TORC2、HNF-4α、PGC-1α等的参与,最后将信号传达至糖异生的2个关键性限速酶基因PECK与G6Pase,起到调控作用。激活的AMPK能抑制糖异生转录因子及相关关键酶的有效表达,阻止肝脏发生糖异生,进而下降血糖浓度。本文旨在讨论与总结AMPK在肝脏糖脂代谢中的作用,重点分析AMPK与肝脏糖异生信号通路转录因子之间的联系。展开更多
Diabetes-associated liver injury becomes a dominant hepatopathy,leading to hepatic failure worldwide.The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1(G-Rh1)on liver injury induced...Diabetes-associated liver injury becomes a dominant hepatopathy,leading to hepatic failure worldwide.The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1(G-Rh1)on liver injury induced by T2DM.A T2DM model was established using C57BL/6 mice through feeding with HFD followed by injection with streptozotocin at 100 mg·kg^(−1).Then the mice were continuously administered with G-Rh1(5 and 10 mg·kg^(−1)),to explore the protective effects of G-Rh1 against liver injury.Results showed that G-Rh1 exerted significant effects on maintaining the levels of FBG and insulin,and ameliorated the increased levels of TG,TC and LDL-C induced by T2DM.Moreover,apoptosis in liver tissue was relieved by G-Rh1,according to histological analysis.Particularly,in diabetic mice,it was observed that not only the increased secretion of G6Pase and PEPCK in the gluconeogenesis pathway,but also inflammatory factors including NF-κB and NLRP3 were suppressed by G-Rh1 treatment.Furthermore,the underlying mechanisms by which G-Rh1 exhibited ameliorative effects was associated with its capacity to inhibit the activation of the Akt/FoxO1 signaling pathway induced by T2DM.Taken together,our preliminary study demonstrated the potential mechnism of G-Rh1 in protecting the liver against T2DM-induced damage.展开更多
Glycogen storage disease type Ia(GSD-Ia)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-αor G6PC)that is expressed primarily in the liver,kidney,and intestine.G6...Glycogen storage disease type Ia(GSD-Ia)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-αor G6PC)that is expressed primarily in the liver,kidney,and intestine.G6Pase-αcatalyzes the hydrolysis of glucose-6-phosphate(G6P)to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis,and is a key enzyme for endogenous glucose production.The active site of G6Pase-αis inside the endoplasmic reticulum(ER)lumen.For catalysis,the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter(G6PT).The functional coupling of G6Pase-αand G6PT maintains interprandial glucose homeostasis.Dietary therapies for GSD-Ia are available,but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma.Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches,including gene therapy.展开更多
文摘腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)是一种广泛参与多种代谢调节的激酶,是主要的细胞"能量感受器"。AMPK通过α亚基的Thr172发生磷酸化而激活,通过抑制脂质合成相关转录因子以及肝脏糖异生来控制脂质合成以及血糖稳定。肝脏糖异生的调控过程中,通过激素及转录因子如Fox O1、CREB、TORC2、HNF-4α、PGC-1α等的参与,最后将信号传达至糖异生的2个关键性限速酶基因PECK与G6Pase,起到调控作用。激活的AMPK能抑制糖异生转录因子及相关关键酶的有效表达,阻止肝脏发生糖异生,进而下降血糖浓度。本文旨在讨论与总结AMPK在肝脏糖脂代谢中的作用,重点分析AMPK与肝脏糖异生信号通路转录因子之间的联系。
基金supported by Jilin Science&Technology Development Plan(No.20200301037RQ).
文摘Diabetes-associated liver injury becomes a dominant hepatopathy,leading to hepatic failure worldwide.The current study was designed to evaluate the ameliorative effects of ginsenoside Rh1(G-Rh1)on liver injury induced by T2DM.A T2DM model was established using C57BL/6 mice through feeding with HFD followed by injection with streptozotocin at 100 mg·kg^(−1).Then the mice were continuously administered with G-Rh1(5 and 10 mg·kg^(−1)),to explore the protective effects of G-Rh1 against liver injury.Results showed that G-Rh1 exerted significant effects on maintaining the levels of FBG and insulin,and ameliorated the increased levels of TG,TC and LDL-C induced by T2DM.Moreover,apoptosis in liver tissue was relieved by G-Rh1,according to histological analysis.Particularly,in diabetic mice,it was observed that not only the increased secretion of G6Pase and PEPCK in the gluconeogenesis pathway,but also inflammatory factors including NF-κB and NLRP3 were suppressed by G-Rh1 treatment.Furthermore,the underlying mechanisms by which G-Rh1 exhibited ameliorative effects was associated with its capacity to inhibit the activation of the Akt/FoxO1 signaling pathway induced by T2DM.Taken together,our preliminary study demonstrated the potential mechnism of G-Rh1 in protecting the liver against T2DM-induced damage.
基金This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development,National Institutes of Health(HD000912-38).
文摘Glycogen storage disease type Ia(GSD-Ia)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-αor G6PC)that is expressed primarily in the liver,kidney,and intestine.G6Pase-αcatalyzes the hydrolysis of glucose-6-phosphate(G6P)to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis,and is a key enzyme for endogenous glucose production.The active site of G6Pase-αis inside the endoplasmic reticulum(ER)lumen.For catalysis,the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter(G6PT).The functional coupling of G6Pase-αand G6PT maintains interprandial glucose homeostasis.Dietary therapies for GSD-Ia are available,but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma.Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches,including gene therapy.
