Early reduction in insulin-like growth factor gene expression in diabetic nerve

Diabetic neuropathy is a common and disabling complication of diabetes mellitus whose pathogenesis remains unknown. Insulin-like growth factors (IGFs) have been recently implicated in the development and maintenance of the peripheral nervous system, and circulating IGF levels are decreased in experimental and clinical diabetes. Therefore, we tested the hypothesis that IGF gene expression is reduced in peripheral nerves early after the onset of diabetes. Sciatic nerves from nondiabetic and streptozotocin-treated rats were removed 5-7 days after the induction of diabetes. RNA was isolated and analyzed by Northern and slot blots. IGF-I mRNA content was significantly decreased per milligram wet weight nerve (P < 0.025) as well as per poly(A)+ RNA (P < 0.01) in diabetic vs nondiabetic nerves. Likewise, the amount of IGF-II mRNA was significantly decreased per milligram wet weight nerve (P < 0.01) as well as per poly(A)+ RNA (P < 0.005). These effects were selective because histone 3.3 mRNA content, as well as poly(A)+ mRNA content, per milligram nerve were unchanged. Insulin treatment partially prevented this decline in IGF-I and IGF-II mRNA levels. The diminished IGF mRNA content is one of the earliest biochemical abnormalities to be observed in the diabetic nerve, supporting the hypothesis that a reduction in IGF activity in diabetic nerves precedes and contributes to the development of neuropathy.