Zhuang H X, Snyder C K, Pu S F, Ishii D N
Department of Physiology, Colorado State University, Fort Collins 80523, USA.
Exp Neurol. 1996 Aug;140(2):198-205. doi: 10.1006/exnr.1996.0129.
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.
糖尿病性神经病变是一种使人衰弱的疾病，其病因尚不清楚。一种新理论认为，神经病变可能是由于糖尿病导致神经营养性胰岛素样生长因子（IGF）活性丧失，并叠加了因衰老而导致的缓慢持续丧失的结果。最近对IGF-I和IGF-II基因表达在糖尿病神经中降低这一预测进行了测试和验证。在此，我们测试了IGF给药可预防或逆转糖尿病性感觉神经病变这一预测。皮下输注IGF-I或IGF-II而非赋形剂，可使链脲佐菌素诱导的糖尿病大鼠的痛觉过敏进展停止（P<0.01）。此外，在用IGFs治疗糖尿病大鼠后2周内，感觉神经再生受损得到部分逆转（P<0.01）。每日皮下注射IGF也可预防再生受损。尽管血糖持续升高和体重减轻，但低剂量的IGF替代治疗仍有效。这些结果表明，IGF替代疗法可独立于高血糖或体重减轻而逆转或预防糖尿病性感觉神经病变。
