The Investigation of Relationship Between Na+/K+ ATPase Enzyme Activity, ATP1A1 Gene Polymorphism and C-Peptide in Type 2 Diabetic Patients with Neuropathy

Objectives: Na+/K+-ATPase is encoded by various genes, of which the ATP1A1 gene is expressed predominantly in peripheral nerves and in erythrocytes. We investigated whether the ATP1A1 polymorphism is associated with Na+/K+-ATPase activity modifications in healthy subjects and in type 2 diabetic patients with polyneuropathy. We also tested whether C-peptide level could influence the relationship between ATP1A1 polymorphism and Na+/K+-ATPase activity. Methods: Na+/K+-ATPase polymorphism has been determined by using polymerase-chain reactions and restriction fragment length polymorphism methods. The erythrocyte membrane Na+/K+-ATPase activity measurement was performed with modified Kitao-Hattori method. C-peptide measurements were performed using competitive chemiluminesence enzyme immunoassay method. Results: Na+/K+-ATPase activity was significantly lower in diabetic polyneuropathic patients than in healthy subjects. Correlation between C-peptide levels and Na+/K+-ATPase activity was not detected. All diabetic patients with polyneuropathy and healthy controls were homozygous for the unrestricted allele. Conclusion: Oxidative stress which develops in diabetes causes lipid peroxidation in the membrane and consequently Na+/K+-ATPase activity decreases. Low enzymatic activity leads to decrease in nerve conduction velocity. Therefore, we believe that better regulation of diabetes can abrogate complications and prevent the development of neuropathy.