Effect Of β-Casomorphin7 Or Casein Peptides On Blood Glucose And Oxidative Stress Of The Diabetic Rats

This study was focused on the effects and mechanisms ofβ-casomorphin7 or casein peptides on blood glucose and oxidative stress in diabetic rats. The research consists of two parts:Experiment 1. Effects ofβ-casomorphin7 or casein peptides on the oxidative stress and protective effects of pancreas in the diabetic ratsMethods:Fifty male SD rats were used for this study. The animals were divided into two groups:a nondiabetic control (n= 8) and a diabetic group (n= 42). STZ was administered intraperitoneally (i.p.) at a single dose of 60 mg·kg-1 to diabetic group(The rats were overnight fasting before i.p.). The control rats were only injected with the citrate buffer.24h and 72h after STZ treatment, development of diabetes was confirmed by measuring blood glucose levels. The rats with blood glucose level 11.1 mmol·L-1 or higher were considered to be diabetic and were used in the experiment. The diabetic rats (n= 32) were randomly divided into four groups:positive control (distilled water treated diabetic rats);β-CM7 (β-CM7 treated diabetic rats); casein peptides (casein peptides treated diabetic rats); casein (casein treated diabetic rats). Every 12h the rats were lavaged. Every 3 days of experimentation, blood samples were collected for biochemical estimations. After 15 days the animals were deprived of food overnight and sacrificed by cervical dislocation. Blood was collected in sterilized tubes with the anticoagulant. Then the liver, heart, leg muscle and small intestine mucous membrane were removed. Observe changes of the blood glucose level, the hormonal level, glycogen and enzymic activity of small intestine mucous membrane. Results:The results showed after 15 days oral administration ofβ-casomorphin 7 or casein peptides, the elevated blood glucose level was reduced (19.5 m mol·L-1,13.9 m mol·L-1&13.5 m mol·L-1). Oral administration ofβ-CM7 or casein peptides to diabetic rats showed an increase in the level of plasma insulin (2.69±0.94μIU·ml-1,3.82±1.13μIU·ml-1&4.11±1.07μIU·ml-1), the elevated plasma glucagon level (301.00±60.04 pg·ml-1,258.53±57.28 pg·ml-1&269.77±25.50 pg·ml-1, P<0.05) was markedly reduced by the oral administration ofβ-CM7 or casein peptides compared with positive control rats. Oral administration ofβ-CM7 to diabetic rats showed markedly an increase in the level of liver glycogen (5.77±2.36&6.60±3.30 mg·g-1) and cardiac muscle glycogen (0.51±0.15 mg·g-1& 1.10±0.39 mg·g-1). Oral administration of casein peptides to diabetic rats showed an increase in the level of cardiac muscle glycogen (0.51±0.15&1.26±0.36 mg·g-1)and leg muscle glycogen (0.52±0.18 mg·g-1& 0.61±0.08 mg·g-1).The small intestine mucous membrane glucosidase and Na+-K+-ATPase activity of P-CM7 or casein peptides treated diabetic rats were as same as those of the positive control rats. Conclusion:The results of the present study suggested that p-casomorphin-7 or casein peptides can decrease the blood glucose by elevating insulin secretion or promoting glycogen synthesis. Hypoglycemic effect of casein itself is not.Experiment 2.Effects ofβ-casomorphin7 or casein peptides on the oxidative stress of pancreas in the diabetic ratsMethods:we obtained the plasma and pancreas in the rats of the previous experiment, observed changes of the plasma and pancreas SOD, GSH-Px, CAT activity and MDA level, analysised the NO level and changes of NF-κB, iNOS mRNA in the pancreas. Results:1) The results showed the plasma and pancreas MDA level of the positive control rats were markedly increased compared with control rats, oral administration ofβ-casomorphin 7 or casein peptides, the plasma and pancreas MDA level were markedly decreased compared with positive control rats (P<0.05).2) The SOD&CAT activity of plasma in the positive control rats were markedly increased compared with control rats, oral administration ofβ-casomorphin7 or casein peptides, the SOD&CAT activity of plasma were markedly increased compared with positive control rats (P<0.05).3) The SOD&GSH-Px activity of pancreas in the positive control rats were markedly increased compared with control rats, oral administration ofβ-casomorphin7 or casein peptides, the GSH-Px&CAT activity of pancreas were markedly increased compared with positive control rats (P<0.05).4) The pancreas NO level of the positive control rats were markedly increased compared with control rats, oral administration ofβ-casomorphin7 or casein peptides, the pancreas NO level were markedly decreased compared with positive control rats (P<0.05). While the plasma&pancreas antioxidative stress enzymic activity, MDA, NO of casein treated diabetic rats were as same as those of the positive control rats. Conclusion:1) The high blood glucose in diabetic rats induced the serious oxidative stress.β-casomorphin7 or casein peptides can decrease the oxidative stress of the organism by elevating the activity of enzymatic antioxidants. The effects of casein have an advantage toβ-casomorphin7.2)β-casomorphin7 or casein peptides can decrease the pancreas oxidative stress by elevating the activity of enzymatic antioxidants and decreasing the NO level and injuries in pancreas by inhibiting NF-κB-iNOS-NO pathway. This may be one of the mechanism thatβ-casomorphin7 or casein peptides can elevate insulin secretion.3) The casein doesn't have antioxidative stress or protective effects in pancreas.