The Degradation Of BCAAS In GK Rats Liver And The Key Genes In The Pathway

The prevalence of diabetes is rising gradually in recent years,becoming the third highest prevalence non-communicable disease,following the cardiovascular disease and malignant tumors.T2 D is a complex endocrine and metabolic disease with many complications,high prevalence,long period of treatment and high cost.Therefore,the treatment of T2 D is a complex and challenging task.Type 1 diabetes(T1D)and type 2 diabetes(T2D)are the most common forms of diabetes.T2 D is characterized by glucose intolerance caused by hyperglycemia.Among the diabetic individuals T2 D patients is more than 90% of diabeteic patients.The adult morbidity of T2 D is 11.6% in China,and total patients has reached 114 million.The number of T2 D patients in China accounts for one third of world's diabetic patients.Besides,the non-obesity T2 D patients is up to 70% of total number in China and Japan.Therefore,more attention shoud be paied to non-obesity T2 D in China even in Asia,especially the mechanisms of early prevention and control.Over the past few decades,researchers have focused on the mechanisms of glucose intolerance in peripheral tissue.And the mechanism of insulin resistance in obesity T2 D have been studied clearly.However,the gradually rising prevelnce has not been prevented.It has been reported that plasma branched chain amino acids(BCAAs;leucine,isoleucine,valine)concertration is significant higher in T2 D patients in early studies,and such increases existed for many years before developing T2 D.Such increase of BCAAs has been confirmed by obesity T2 D animal models.But the relevant research of BCAAs in non-obesity animal models has been rarely reported.We focus on the degradation of BCAAs and the key genes in the pathway,by analysis the gene expression profiles of human,mouse and rats,analysis the functional cluster and the analysis of KEGG,and taking the metabolites related to T2 D into account,in our research.In this experiment,we detected the concentration of BCAAs in spontaneous non-obesity rats T2D-GK rats by liquid chromatography tandem mass spectrometry(LC/MS)and expression of BCKDHA and BCKDK(branched chain ?-keto acid dehydrogenase kinase)in livers by real-time quantitative PCR.BCKDHA is the rate-limiting enzyme of BCAAs degradation.And then compared mechanism in obesity T2 D animal models with non-obesity T2 D animal models.In this experiment,we found the BCAAs concentration of fourth week and eighth week in GK rats is significant lower than Wistar rats.Meanwhile,the expression of BCKDHA is higher in GK rats liver than Wistar rats.And the expression of BCKDK is lower in GK rats liver than Wistar rats.Therefore,we speculated that the BCAAs degradation level is higher in GK rats than Wistar rats.Our experiment revealed that the regulating mechanism of BCAAs was differernt in obesity T2 D animal models and non-obesity T2 D animal models.Wheather BCAAs could be used as a marker for early T2 D risk assessment also needed further research.Our experiment further reveals the mechanism of BCAAs degradation and also provides the theoretical basis in preventing T2D.