| Diabetes metilltus is one of the life-threatening epidemic diseases , which forms the third death rate just descending from the cardiovascular diseases , cerebrovascular diseases and cancer . The high mortality and disablity rate characterizes the diabetic complication. The diabetic vascular complication is comprised of macrovascular diseases and microvascular diseases and there are some interesting and subtle differences between them. It is generally believed that macrovascular and microvascular complications coexist in type 2 diabetes , while the former is the main fatal reason, however, in type 1 diabetes the later is more dangerous, and in most cases, the microvascular complications in type 1 diabetes is obviously faster developed than that in type 2 diabetes.There is now no satisfactory explanation to this phenomenon, but from these clues we might conclude that the pathogenesis of the complication in type 1 and type 2 diabetes might be somewhat different. Recently it is reported that the diabetic patients who preserve some residual pancreas islets were more unlikely to capture the microvascular complications than those whose pancreas are completely destroyed , despite almost the same glycemia condition controlled by insulin. It was once believed that this is probably caused by the superiority of endogenesis insulin to exogenesis insulin, but with the finding of the biological effect of C-peptide, C-peptide's effect is obviously more reasonable.Connecting peptide (C-peptide ) is a product of proinsulin processed to insulin and is secreted by the pancreatic beta cells in equimolar amounts along with insulin. It was thought that C-peptide's main physiological role was in facilitating the folding of the proinsulin molecule in a manner that allowed for the appropriate formation of the disulfide bonds between the cysteine residues of the A- and B-chains of insulin. Recently, however it has been demonstrated that C-peptide treatment of type 1 diabetic patients resulted in improved complication conditions. The hypothesis of C-peptide might cause a revolution in the treatment of type 1 diabetes and the type 2 diabetic patients with complete islets destruction: the combination use of insulin and C-peptide, a mixture that much more Natural, will ultimately replace the conventional use of insulin. The aim of this study to investigate the different activity of Na/K-ATPase of erythrocyte membrane between the Tl and T2 diabetes and the relationship with concentration of C-peptide; to testify the biofunction of the C-peptide and C-peptide-K. Materials and methodsThe study is designed to study the C-peptide's biofunction and its therapeutical effect in the diabetic microvascular complication . The research consists of case-control clinical epidemic study and experiment in vitro. The subjects of the study is comprised of T1DM group, T2DM group, and control group; the T2DM group is subdivided into sulfonylureas group and insulin group. The blood samples were taken and anti-coagulated when the subjects are under fasted condition. The concentration of the plasm C-peptide, plasm insulin, HBAic, etc were measured at the same time; in vitro, the erythrocyte of the type 1 diabetic patients were incubated with C-peptide( or C-peptide-K) of varied concentrations and (or) insulin. The relation between the concentration of C-peptide in plasm and the Na/K-ATPase activity of the erythrocyte and nitrous oxide concentration in plasm as well were analysed to testify the biological effect of the C-peptide. Results1. The Na/K-ATPase activity of the erythrocyte membrane in type 1 diabetic patients is significantly lower than that of type 2 diabetes and health control group(P<0.05), while there is no significant difference in the later two groups (P>0.05) .The plasm level of nitrous oxide in type 1 group is lower than that of type 2 diabetes and health control group (P<0.05) , and there is no significant difference in the later two groups (P>0.05) .2. In type 2 diabetes , the Na/K-ATPase activity of the erythrocyte membrane and the plasm concentration of nitrous oxide in sulfonylureas group are significantly higher that of insulin group (P<0.05) .3. In type 2 diabetes the Na/K-ATPase activity of the erythrocyte is negatively correlated with the course (r=-0.598, P=0.000), the age (r=-0.307, P=0.000) and positively correlated with the concentration of C-peptide (r=0.339, P<0.005)and insulin level(r=0.577, P=0.000) in plasm. The concentration of the nitric oxide in type 2 diabetes has a negative correlation with the course (r=-0.406, P=0.000) and a positive correlation with the blood glucose (r=0.238, P<0.05).4. The Na/K-ATPase activity of the erythrocyte in type 1 diabetes is positively correlated with the concentration of C-peptide (r=0.790, P=0.000) and insulin level (r=0.839, P=0.000) in plasm. The concentration of the nitric oxide in plasm of type 2 diabetes has a positive correlation with the concentration of C-peptide (r=0.883, P=0.000) and insulin level (r=0.806, P=0.000) in plasm.5. Stepwise regression aNalysis results suggested that the course and the level of insulin in plasm are the most influential factors that affects the the Na/K-ATPase activity of the erythrocyte membrane in type 2 diabetes.6. In type 2 diabetic group the course is negatively correlated with the concentration of C-peptide in plasm (r= — 0.368, P<0.01) and no similar correlation is found in type 1 diabetic group.7. Severity of the diabetic nephropathy and diabetic retinopathy is negatively correlated with the concentration of C-peptide in plasm.8. In vitro, the Na/K-ATPase activity of the erythrocyte membrane is significantly promoted after the blood sample from the type 1 diabetic patients were incubated with C-peptide or C-peptide-K solution of varied concentration with or without insulin. No dose-dependent effect were found in this phenomenon. C-peptide-K has a biofunctionlike the C-peptide. Conclusions1. The Na/K-ATPase activity of the erythrocyte and the plasm concentration of nitrid oxide in type 1 diabetic patients is significantly lower than that in type 2 diabetic patients, the Na/K-ATPase activity of the erythrocyte and the plasm concentration of nitrid oxide is positively correlated with the C-peptide concentration in plasm, which suggests that the lack of C-peptide may play an important role in the pathological state in microvascular circulation.2. In vitro, the Na/K-ATPase activity of the erythrocyte membrane is significantly promoted after incubated with C-peptide solution and the promotion was enhanced significantly by the cooperation with insulin; the analog of C-peptide, C-peptide-K, possesses the similar biological effect like C-peptide.3. In type 2 diabetes the Na/K-ATPase activity of the erythrocyte and the plasm concentration of nitrid oxide in sulfonylureas group are significantly higher than that of insulin group. The fact suggested that the C-peptide might play an important role in improving the Na/K-ATPase activity of the erythrocyte and the plasm concentration of nitrid oxide.4. The Na/K-ATPase activity of the erythrocyte and the plasm concentration of nitrous oxide in diabetic patients is positively correlated with the function of the islets . The microvascular complication in diabetes might accelerate with prolonged course and gradual loss of the islets. C-peptide has a protective effect on the kidney and retna in diabetes.
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