REDUCED INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RNA CONTENT IN LIVER, ADRENAL-GLANDS AND SPINAL-CORD OF DIABETIC RATS

Circulating insulin-like growth factor I (IGF-I) concentrations are known to be reduced in experimental and clinical diabetes mellitus. The IGF-I mRNA content was measured in several tissues of rats treated with streptozotocin to determine whether a correlation with neuropathy could be found. IGF-I mRNA content was sharply reduced relative to total and poly(A)(+) RNA in diabetic liver and adrenal glands. In contrast, histone 3.3 mRNA content was not significantly reduced relative to poly(A)(+) RNA in liver, and alpha-tubulin mRNA content instead was increased in adrenal glands, showing that the decline in IGF-I mRNAs in these tissues was selective. In addition, spinal cord IGF-I mRNA content was significantly reduced per tissue, total RNA, and poly(A)(+) RNA after 1 and 2 weeks of diabetes. This was correlated with a concurrent and significant decrease in conduction velocity in both spinal cord and peripheral nerves in a separate study. The decline in liver and spinal cord IGF-I mRNA was not due to streptozotocin toxicity, because it was significantly opposed by insulin which was continuously infused beginning the day after diabetes induction. These results, when taken together with those of others, indicate that the reduction in IGF-I mRNA content may be widespread among diabetic tissues, and might contribute in part to certain syndromes of diabetes, such as neuropathy.