) RAT( و ارتباط آن با عوارض ثانويه ديابت در موش آزمايشگاهي )PKC( C بررسي فعاليت پروتيين كيناز

Protein Kinase C Activity and Its Relationship with Diabetic Complications in Rats

Diabetes is a prevalent disease in our country as it is worldwide. The rat is a suitable animal model for these studies. Protein kinase C is an enzyme which in its inactive form is located in the cytoplasm, but when activated (with calcium and phospholipid), translocate to the plasma membrane and phosphorylate the target proteins. Effects of this protein kinase and its isoenzymes in diabetic complications has been implicated. In this study, diabetes was induced with streptozotocin in the rat, and the effect of nifedipine (a calcium channel blocker), and polymyxin B sulphate (protein kinase C inhibitor) was investigated. The results showed that the levels of the, urea (two-fold), creatinine (60%), triglyceride (two-fold) and liver enzymes (two-fold) were significantly increase in the diabetic group. While in the other diabetic group, which was treated with oral nifedipine, although urea and creatinine Ievels were increased, had no increased in enzyme levels significantly different from those of the control group. The diabetic group treated with polymyxin had metabolites and enzyme levels equal to the control group except glucose level which was increased and liver glycogen storage which was decreased significantly. Protein kinase C activity in the cytoplasm of untreated diabetic group liver was increased comparing to its control group (573 ± 56 vs 400 ± 62). The enzyme activity in the plasma membranes of untreated and nifedipine treated diabetic groups was significantly increased, but in the polymyxin treated diabetic group the enzyme activity was close to the control group. Enzyme activity in the kidney cell membranes was significantly increased only in the untreated diabetic group. These results show that polymyxin is more effective than nifedipine against protein kinase C activity in diabetic complications. In conclusion, the results of this and other studies show that protein kinase C contributes to diabetic complications. We hope that future drug designers will target protein kinase C isozymes with specific inhibitors.