Insulin-Ameliorated Peripheral Motor Neuropathy in Spontaneously Diabetic WBN/Kob Rats

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  • OZAKI Kiyokazu
    Department of Pathology, Setsunan University, 45–1 Nagaotohge-cho, Hirakata, Osaka 573–0101, Japan
  • YAMANO Shotaro
    Department of Pathology, Osaka City University Graduate School of Medicine, 1–4–3 Asahi-machi, Abeno-ku, Osaka 545–8585, Japan
  • MATSUURA Tetsuro
    Department of Pathology, Setsunan University, 45–1 Nagaotohge-cho, Hirakata, Osaka 573–0101, Japan
  • NARAMA Isao
    Department of Pathology, Setsunan University, 45–1 Nagaotohge-cho, Hirakata, Osaka 573–0101, Japan

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Rodent models of diabetes develop a slowing of nerve conduction velocity and mild axonal atrophy, but generally lack overt degenerative neuropathy. Spontaneously diabetic Wistar Bonn Kobori (WBN/Kob) rats develop severe diabetic peripheral motor neuropathy with a slowing of nerve conduction velocity. We examined the effect of glycemic control, using insulin implant, on neuropathic changes in these rats. Animals were divided into 2 groups: WBN group (spontaneously occurring diabetes rats) and WBN + insulin group (spontaneously occurring diabetes rats treated with insulin implants until 90 weeks of age). Conduction velocity was measured in sciatic–tibial motor nerves. These nerves also underwent qualitative and quantitative histomorphologic analysis. Mild to severe hyperglycemia (>200 mg/dl) and glycosuria (>100 mg/dl) were observed in the WBN group. In contrast, the blood glucose level of the WBN + insulin group fluctuated between normoglycemia (<200 mg/dl) and hyperglycemia. Conduction velocity significantly decreased in WBN group compared with WBN + insulin group. Morphologic analysis of the sciatic and tibial nerves of WBN group showed severe changes, including axonal degeneration, myelin distention, endoneurial fibrosis and microangiopathy. Insulin treatment corrected these changes without microangiopathy. These results suggest that insulin could decrease axonal atrophy and myelin distension of peripheral nerve in diabetic WBN/Kob rats. Observation of WBN/Kob rats revealed changes of axon, myelin and capillary caused by diabetes, thus indicating that this animal is a suitable model for investigating diabetic peripheral neuropathy.

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