Effects of long-term treatment with α-glucosidase inhibitor on the peripheral nerve function and structure in Goto-Kakizaki rats: a genetic model for Type 2 diabetes
✍ Scribed by Ryuichi Wada; Motoi Koyama; Hiroki Mizukami; Hiroyuki Odaka; Hitoshi Ikeda; Soroku Yagihashi
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 116 KB
- Volume
- 15
- Category
- Article
- ISSN
- 1520-7552
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✦ Synopsis
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 a-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 signi®cantly 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 ®ber studies revealed a higher incidence of ®bers with paranodal, segmental demyelination and axonal degeneration in GK rats. Vg treatment signi®cantly inhibited the development of these nerve-®ber 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.