The Effect And Mechanism Of DMDD On Type2Diabetes Glucose And Lipid Metabolism And Diabetic Nephropathy

Type2diabetes mellitus is a kind of metabolic disorder due to insulinresistance andinsulin-the glucose，lipid and protein metabolic disordersyndrome accompanying hyperlipidemia．In recent years，the morbidityof diabetes in the world is increasing year afteryear all over the worldbecause of the combination of elevated living standards，change in theeating habits，reduced manual labor and Increased rates of obesity.Diabete becomes oneof the mostserious illness threatening human healthafter cardiovascular and cerebrovascular disease and cancer.Therefore，itis urgent to look for some safe and effective methods toprevent and treatthe diabetes.The roots of Averrhoa carambola L.（Oxalidaceae） have a longhistory of medicaluse in traditional Chinese medicine for treatingdiabetes and diabetic nephropathy.2-dodecyl-6-methoxycyclohexa-2，5-diene-1，4-dione （DMDD） was isolated from thetuberous roots ofAverrhoa carambola L.Objective:The purpose of this study was to investigate the the effectsof DMDD on blood glucose，blood lipid，glucolipid metabolism in liverand beneficial effect of DMDD on the advanced glycationend-product-mediated renalinjury in type2diabetic KKAy mice with regard to prove its efficacy by local traditional practitioners in thetreatment of diabeties.Methods:KKAy micewere orally administrated DMDD （12.5，25，50mg/kg body weight/d） oraminoguanidine （200mg/kg bodyweight/d） for8weeks. The body weight， death， FBG， totalcholesterol（TC），triglyceride （TG）， low density，lipoprotein-cholesterol （LDL-C），high density lipoprotein-cholesterol（HDL-C），apolipoprotein（Apo）AI，ApoB，free fatty acid（FFA），total lipidase，tumor necrosis factor alpha（TNF-α）of the mice wererecorded during these days. Then， the mice were sacrificed， and theirkidneys were harvested for histopathological and immunohistochemical（RAGE，NF-κB， TGF-β1，CML） analysis.Results:Fasting blood glucose，HbAlc，TG，TC，LDL-C，ApoB andFFA in type2diabetic KKAy mice were all sjgnif!icantly higher thanthat of the C57BL/6J mice，while HDL-C and ApoAI levels weresignificantly lower． DMDD markedly decreased blood glucose，HbAlc，TG， TC，LDL-C，ApoB andFFA contents of type2diabetic KKAymice，while increased HDL-C and ApoAI1evels．DMDD increased thedeclined glycogen content in1iver of diabetic mice，while decreased theaugmented FFA and TG1evels in diabetic tissues． DMDD increasedSOD activity and decreased MDA content．DMDD significantly declinedFFA，MDA， SOD and TNF-α contents in serum and adipose tissue ofdiabetic mice， while increased adiponectin level and total lipidase，SOD activities．Renal AGE formation， and the expression of relatedproteins， such as the AGE receptor， nuclearfactor-κB， transforminggrowth factor-β1， and Nε-（carboxymethyl）lysine， were markedly decreased by DMDD. Diabetes-dependent alterations in proteinuria，serum creatinine， creatinine clearance， and serum urea-N andglomerular mesangial matrix expansion were attenuated after treatmentwith DMDD for8weeks. The activities of superoxide dismutase andglutathione peroxidase， which were reduced in the kidneys of KKAymice， were enhanced by DMDD.Conclusions: These findings suggest that DMDD may inhibit theprogression of diabetic nephropathy and may be a therapeutic agent forregulating several pharmacological targets in treating diabeties.