Insulin-like growth factors reverse or arrest diabetic neuropathy: effects on hyperalgesia and impaired nerve regeneration in rats.
Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. A new theory proposes that neuropathy may arise as a consequence of loss of neurotrophic insulin-like growth factor (IGF) activity due to diabetes, superimposed on a slow continual loss due to aging. The prediction that IGF-I and IGF-II gene expression are reduced in diabetic nerves was recently tested and validated. Here we tested the prediction that IGF administration can prevent or reverse diabetic sensory neuropathy. Subcutaneous infusion of IGF-I or IGF-II, but not vehicle, halted (P < 0.01) the progression of hyperalgesia in streptozotocin-diabetic rats. Moreover, impaired sensory nerve regeneration was partially reversed within 2 weeks after treatment of diabetic rats with IGFs (P < 0.01). Impaired regeneration could also be prevented by daily subcutaneous IGF injections. The low replacement doses of IGFs were effective despite unabated hyperglycemia and weight loss. These results show that IGF replacement therapy can reverse or prevent diabetic sensory neuropathy independently of hyperglycemia or weight loss.
Zhuang
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HX
Department of Physiology, Colorado State University, Fort Collins 80523, USA.
Snyder
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CK
Pu
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Ishii
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DN
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D006930:Hyperalgesia / Q000188:drug therapy; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II