Superoxide dismutase (SOD) is an enzyme found in most food sources, might be a candidate to reduce oxidative damage to intestinal barrier, thereby ameliorating the vicious circle between hyperglycemia and the oxidative damage. Here we report the oral administration of SOD, liposome-embedded SOD (L-SOD), and SOD hydrolysate to type 2 diabetic model rats to confirm this hypothesis. Oxidative damage severity in model rat intestine was indicated by malondialdehyde level, GSSG/GSH ratio, and antioxidant enzyme activity. The damage was significantly repaired by L-SOD. Furthermore, blood glucose and related indexes correlated well not only with oxidative damage results but also with indexes indicating physical intestinal damage such as colon density, H&E staining, immunohistochemical analysis of the tight junction proteins occludin and ZO-1 in the colon, as well as lipopolysaccharide and related inflammatory cytokine levels. The order of the magnitude of the effects of these SOD preparations was L-SOD > SOD > SOD hydrolysate. These data indicate that orally administered SOD can exhibit glucose-lowering effect via targeting the intestine of diabetic rats and systemic lipopolysaccharide influx.

Hypoglycemic Effect of Oral Administered Superoxide Dismutase on Type 2 Diabetes via reduction of glucogan and insulin resistance Background & Objective: Superoxide dismutase (SOD) is carefully used in food industry for the concern of its easy degradation and difficult adsorption in digestive tract, although it plays central role in antioxidant system. It is previous reported that orally administered SOD was effective in alleviating hyperglycemia, cerebral ischemia-reperfusion and chronic hepatitis. This work aimed to investigate in-depth the hypoglycaemic effect and possible mechanism of orally administered SOD in the model of type 2 diabetic rats. Methods:The model of type 2 diabetic rats were divided into 6 groups and orally administered with different Cu/Zn-SOD (abbreviated as SOD) samples and negative or positive controls. The 6 groups included SOD, SOD hydrolysate (pepsin-treated SOD), L-SOD (liposome-embedded SOD), model group and metformin positive groups, as well as normal group. Results of the body weight, serum indexes (including blood glucose, glycated albumin, insulin, glucagon, AMPK, MDA), SOD enzymatic activity in organs (liver, heart, kidney, skeletal muscle, spleen, and pancreas) as well as intestinal density and HE staining were measured to evaluate the hypoglycemic effect and possible mechanism. Results: SOD showed substantial hypoglycemic effect and improved serum indicators. Moreover, L-SOD group exhibited better effect than SOD group, though the effect of SOD hydrolysate was not obvious. Colon density and HE staining showed obvious intestinal injury in the model group, and SOD was beneficial to repair intestinal structural integrity. Furthermore, the reparative effect of SOD was much better than that of the SOD hydrolysate, but not as good as that of the L-SOD. The SOD enzymatic activity of tissues was positively correlated with the curative effect of three kinds of SOD samples. The contents of serum MDA were negatively correlated with the curative effect. Compared with the model group, the insulin resistance index of SOD group, L-SOD group and positive group were significantly reduced; and glucagon significantly decreased by 68.38, 77.50 and 65.01%, respectively. Conclusion: Oral SOD showed obvious hypoglycemic effect on type 2 diabetic rats, and liposome could improve this effect. The mechanism may be that SOD effectively reduces intestinal injury, so as to reduce glucongen and insulin resistance index.