The Research On Characterization And The Auxiliary Hypoglycemic Effect Of TAT-SOD

Diabetes mellitus and its complications seriously affect human health.Oxidative stress is generally considered as a common pathway for the pathogenesis of diabetes mellitus and its complications.Superoxide dismutase(SOD)is the most important antioxidant enzyme in the body,which is expected to play an important role in the treatment of diabetes.However,the clinical application of SOD is limited because it is a macromolecular protein and its membrane permeability is poor,so it can only scavenge the free radicals outside the membrane.TAT-SOD is a fusion protein of the TAT protein transduction domain and SOD,which can improve the above problems.The Auxiliary hypoglycemic effects of TAT-SOD and natural SOD are compared on the basis of experimental analysis of physical and chemical properties of TAT-SOD.The physicochemical property of TAT-SOD was investigated by measuring the effect of TAT-SOD on enzyme activity at different temperatures and pH and its stability under pepsin digestion.Then we compared the effects of the same dose of natural SOD and TAT-SOD,different doses of TAT-SOD and different administration route of TAT-SOD in of type Ⅰ and type Ⅱ diabetic rats.Several parameters were recorded and compared including the body weight,blood glucose,Oral glucose tolerance test(OGTT),SOD level in different tissue,plasma insulin(INS),glucagon(GLUCA),AMP-activated protein kinase(AMPK),malondialdehyde(MDA),glycosylated albumin(GA)and lipid levels.The results showed that both SOD and TAT-SOD have significant auxiliary hypoglycemic effects on type Ⅰ and type Ⅱ diabetic model rats,with the TAT-SOD(medium)dose group being the best.The results of treatment of type Ⅰ diabetes found that TAT-SOD was significantly better at controlling body weight and blood glucose than SOD(P<0.05);while in the OGTT test,the effect were comparable;TAT-SOD group and SOD group had similar SOD enzyme activity in the liver,but in the kidney,SOD enzyme activity was significantly higher than that of the latter;In plasma biochemical level,SOD and TAT-SOD could both improve INS and AMPK levels,and TAT-SOD decreased MDA level better than SOD.The results of treatment of type Ⅱdiabetes found that TAT-SOD was equivalent to SOD in weight control;but TAT-SOD was better than SOD in blood glucose control and OGTT(P<0.05),and TAT-SOD significantly reduced the GA Levels(P<0.05);Both SOD and TAT-SOD can reduce MDA and GLUCA,and TAT-SOD is better than SOD in improving INS;TAT-SOD not only significantly increases HDL levels(P<0.05),but also decreases total cholesterol and triglyceride levels(P<0.05)in blood lipid control.The intragastric administration effect was comparable to that of the oral administration,which shows that TAT-SOD can help to lower the blood glucose level under different administration routes.These results indicated that both SOD and TAT-SOD have obvious auxiliary hypoglycemic effect,and the comprehensive effect of TAT-SOD is superior to SOD.These effects may be due to the better membrane translocation ability of TAT-SOD than that of SOD on the digestive tract,and TAT domain further enhances the antioxidant effect of SOD.