Hyperhomocysteinemia stimulates hepatic glucose output and PEPCK expression  

作　　者：Xue Yu Youguang Huang Qiang Hu Lanqing Ma 

机构地区：[1]Department of Cardiology, Beijing Hospital, Beijing 100730, China [2]Department of Biochemistry, Kunming Medical College, Kunming 650031, China [3]Department of Emergency Medicine, The Second Affiliated Hospital, Kunming Medical College, Kunming 650101, China [4]Department of Digestive Diseases, The First Affiliated Hospital, Kunming Medical College, Kunming 650032, China

出　　处：《Acta Biochimica et Biophysica Sinica》2009年第12期1027-1032,共6页生物化学与生物物理学报（英文版）

摘　　要：Homocysteine is an intermediate in the sulfur amino acid metabolism. Recent studies suggested that there might be links between hyperhomocysteinemia and insulin resistance. In the present study, we investigated the effect of homocysteine on glucose metabolism. We demonstrated that the levels of insulin were significantly higher in mice with hyperhomocysteinemia than those in the normal mice after administration of glucose. The effect of insulin on glucose output was significantly blocked in the homocysteine-treated hepatocytes. In addition, the expression of phosphoenolpyruvate carboxykinase （PEPCK） gene was elevated in the liver of mice with hyperhomocysteinemia and primary mouse hepatocytes treated with homocysteine. The action of homocysteine was suppressed by H89, a protein kinase A （PKA） inhibitor. Thus, hyperhomocysteinemia may be considered as a risk factor that contributes to the development of insulin resistance with respect to elev- ated glucose output and upregulation of PEPCK, probably via the PKA pathway. Our study provides a novel mechanistic explanation for the development of insulin resistance in hyperhomocysteinemia.Homocysteine is an intermediate in the sulfur amino acid metabolism. Recent studies suggested that there might be links between hyperhomocysteinemia and insulin resistance. In the present study, we investigated the effect of homocysteine on glucose metabolism. We demonstrated that the levels of insulin were significantly higher in mice with hyperhomocysteinemia than those in the normal mice after administration of glucose. The effect of insulin on glucose output was significantly blocked in the homocysteine-treated hepatocytes. In addition, the expression of phosphoenolpyruvate carboxykinase （PEPCK） gene was elevated in the liver of mice with hyperhomocysteinemia and primary mouse hepatocytes treated with homocysteine. The action of homocysteine was suppressed by H89, a protein kinase A （PKA） inhibitor. Thus, hyperhomocysteinemia may be considered as a risk factor that contributes to the development of insulin resistance with respect to elev- ated glucose output and upregulation of PEPCK, probably via the PKA pathway. Our study provides a novel mechanistic explanation for the development of insulin resistance in hyperhomocysteinemia.

关 键 词：HOMOCYSTEINE insulin resistance phosphoenolpymvate carboxykinase （PEPCK） proteinkinase A 

分 类 号：Q517[生物学—生物化学] TP334.83[自动化与计算机技术—计算机系统结构]