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 poor ly understood. A new theory proposes that neuropathy may arise as a co nsequence of loss of neurotrophic insulin-like growth factor (IGF) act ivity due to diabetes, superimposed on a slow continual loss due to ag ing. The prediction that IGF-I and IGF-II gene expression are reduced in diabetic nerves was recently tested and validated. Here we tested t he 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 streptoz otocin-diabetic rats. Moreover, impaired sensory nerve regeneration wa s partially reversed within 2 weeks after treatment of diabetic rats w ith IGFs (P < 0.01). impaired regeneration could also be prevented by daily subcutaneous IGF injections. The low replacement doses of IGFs w ere effective despite unabated hyperglycemia and weight loss. These re sults show that IGF replacement therapy can reverse or prevent diabeti c sensory neuropathy independently of hyperglycemia or weight loss. (C ) 1996 Academic Press, Inc.