Effects of long-term treatment with alpha-glucosidase inhibitor on the peripheral nerve function and structure in Goto-Kakizaki rats: a genetic model for type 2 diabetes.
키워드
요약
BACKGROUND
Continuous hyperglycemia is implicated in the pathogenesis of chronic diabetic complications. It is not well known, however, how and to what extent the development of neuropathy is inhibited by blood glucose control in subjects with Type 2 diabetes. We investigated therefore the effects of an alpha-glucosidase inhibitor (voglibose; Vg) on neuropathic changes in diabetic Goto-Kakizaki (GK) rats, a genetic model for Type 2 diabetes.
METHODS
Twelve week-old male GK rats were given a diet containing Vg (50 ppm) for 24 weeks and monitored for blood glucose, glycated hemoglobin, motor nerve conduction velocity (MNCV). At the end of the administration period (Na(+), K(+))-ATPase activity and the structure of the peripheral nerves were examined. Age- and sex-matched normal Wistar rats were treated similarly and served as controls.
RESULTS
GK rats showed fasting hyperglycemia after 8 weeks of age, and Vg treatment significantly lowered levels of blood glucose and glycated hemoglobin. Slowing of MNCV to 80% of normal control levels was detected in GK rats. Vg treatment inhibited this delay by 24% at 24 weeks and 57% at 36 weeks of age. Nerve (Na(+), K(+))-ATPase activity was reduced to 80% of normal control levels in GK rats and was restored by Vg treatment. Teased fiber studies revealed a higher incidence of fibers with paranodal, segmental demyelination and axonal degeneration in GK rats. Vg treatment significantly inhibited the development of these nerve-fiber abnormalities.
CONCLUSIONS
Lowering of high blood glucose levels achieved by the use of Vg in GK rats improved MNCV and demyelinative nerve changes with restoration of (Na(+), K(+))-ATPase activity.
