diabetes type 2 pdk4 - Background Type 2 diabetes mellitus T2DM diabetes mellitus type 1 case report is a metabolic disorder characterized by limited metabolic flexibility in the body Such limitation implicates the pyruvate dehydrogenase kinase 4 PDK4 gene Poor nutrition frequently observed among Southeast Asians usually involves excessive intakes of carbohydrates and monosodium glutamate MSG that have been frequently linked to an increased It was found that PDC activation during low to moderateintensity muscle contraction was 2 fold higher in PDK4 knockout mice than in wildtype mice during exercise regardless of the intensity PDK4 mRNA was markedly increased during prolonged exercise and after both shortterm highintensity and prolonged lowintensity exercise in skeletal PDK4 rescues highglucoseinduced senescent fibroblasts and Nature Lower PDK4 expression was found in preadipocytes from obese humans with type 2 diabetes Recent studies have reported that the aberrant methylation of PDK4 promotors was found both in diabetic patients peripheral blood samples 22 and in a mouse model 23 which disturbed PDK4 expression and led to diabetes mellitus The pivotal role of pyruvate dehydrogenase kinases in metabolic Aims Pyruvate dehydrogenase kinase 4 PDK4 plays a crucial role in glucose utilization and lipid metabolism by regulating the pyruvate dehydrogenase complex PDC and is an emerging therapeutic target for type 2 diabetes To date no study has specifically examined the relationship between PDK4 gene polymorphisms and type 2 diabetes or metabolic syndrome Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with In this study we observed PDK4 expression decreased in diabetic skin and fibroblasts but there is literature that states that the level of PDK4 is elevated in patients with type 2 diabetes and In the mouse model of Type 2 diabetes liver insulin receptor substrates 1 and 2 guideline diabetes kidney are deleted and additional knockout of PDK4 gene can improve blood glucose control and glucose tolerance PDK2PDK4 double gene knockout mice cannot tolerate longterm fasting 48 h Because PDK inhibitors have been shown to be effective potential therapeutics in improving glycemic control and type 2 diabetes these kinases warrant more indepth analysis In particular PDK4 proves to be an object of necessary consideration because it is expressed in substantial amounts in skeletal muscle and adipose tissue The STAT5AMediated Induction of Pyruvate Dehydrogenase Kinase 4 Therefore PDKs are attractive targets for the development of medications for treating metabolic diseases especially type 2 diabetes obesity hepatic cirrhosis lactic acidosis and cancers The development of small pharmacochemical s which target the PDKs is an attractive approach for treating metabolic diseases induced by dysregulation Pyruvate Dehydrogenase Kinase 4 Diabetes American Diabetes Association Pyruvate dehydrogenase kinases PDKs an overview toward clinical Association of pyruvate dehydrogenase kinase 4 gene PubMed Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co A 2h treatment of differentiated 3T3F442A adipocytes with rosiglitazone induced PDK4 mRNA 25fold whereas the concentrations of PDK2 and PC mRNAs were unchanged Elevated concentration of plasma NEFA is now recognized as a key factor in the onset of insulin resistance and type 2 diabetes Pyruvate dehydrogenase kinase 4 PDK4 plays a crucial role in glucose utilization and lipid metabolism by regulating the pyruvate dehydrogenase complex PDC and is an emerging therapeutic target for type 2 diabetes To date no study has specifically examined the relationship between PDK4 gene polymorphisms and type 2 diabetes or metabolic syndrome Pyruvate Dehydrogenase Kinases Therapeutic Targets for Diabetes and Exploring dietinduced promoter mediterranean diet diabetes cookbook hypomethylation and PDK4 Springer
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