Insulin-induced hypoglycemic peripheral motor neuropathy in spontaneously diabetic WBN/Kob rats.
Intensive insulin therapy can lead to hypoglycemia, with patients sometimes developing hypoglycemic neuropathy. Spontaneously diabetic Wistar Bonn Kobori (WBN/Kob) rats develop diabetic peripheral motor neuropathy characterized by segmental demyelination and axonal degeneration. We examined the short-term effects of hypoglycemia on neuropathic changes in these rats. Spontaneous diabetic WBN/Kob rats received insulin implants for 40 d and were divided into 3 groups based on blood glucose levels: group N, normoglycemic to slightly hyperglycemic (150 to 250 mg/dL); group H, hypoglycemic to slightly hyperglycemic (50 to 200 mg/dL); and group D, nontreated spontaneously diabetic (350 to 420 mg/dL). Conduction velocity was measured in sciatic-tibial motor nerves; these nerves also underwent qualitative and quantitative histomorphologic analysis. Conduction velocity was not significantly different in N, D, and H groups. Morphologic analysis of the sciatic nerves of H rats showed severe changes, including axonal degeneration, myelin distention, and endoneurial fibrosis, that tended to occur in large, myelinated fibers. N and D rats showed relatively mild changes. The degree and distribution of degenerated nerve fibers in H rats were significantly higher than in N and D rats. These results suggest that hypoglycemia of less than 50 mg/dL induced severe peripheral neuropathy. Hypoglycemic lesions differed from the hyperglycemic lesions in diabetic WBN/Kob rats. This rat strain is an appropriate model for investigating the hypoglycemic peripheral neuropathy that can be associated with a diabetic condition.
Ozaki
Kiyokazu
K
Department of Pathology, Faculty of Pharmaceutical Science, Setsunan University, Osaka, Japan. ozaki@pharm.setsunan.ac.jp
Sano
Tomoya
T
Tsuji
Naho
N
Matsuura
Tetsuro
T
Narama
Isao
I
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004195:Disease Models, Animal; D007003:Hypoglycemia / Q000139:chemically induced* / Q000150:complications; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D016472:Motor Neuron Disease / Q000209:etiology / Q000473:pathology*; D009431:Neural Conduction / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000473:pathology; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin
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