INSULIN-LIKE-GROWTH-FACTOR (IGF) GENE-EXPRESSION IS REDUCED IN NEURALTISSUES AND LIVER FROM RATS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS, AND IGF TREATMENT AMELIORATES DIABETIC NEUROPATHY

Neural disturbances are observed in the peripheral and central nervous systems of patients with insulin-dependent diabetes mellitus (IDDM) a nd non-IDDM (NIDDM). Insulin-like growth factors (IGFs) are neurotroph ic growth factors that can support nerve regeneration and neuronal sur vival in the types of neurons known to be afflicted in diabetes. We te sted the hypotheses that IGF gene expression is reduced in neural tiss ues and liver of spontaneously diabetic obese Zucker (fa/fa) rats and that IGF treatment can prevent neuropathy. There was a significant ear ly reduction in IGF-II mRNA content as measured per mg of wet tissue o r per poly(A)(+) RNA in sciatic nerves, spinal cord and brain from spo ntaneously diabetic obese (fa/fa) vs. nondiabetic lean (+/+) adult rat s. In addition, IGF-l mRNA content was reduced in liver but not nerve or spinal cord oi: NIDDM rats. Pain/pressure thresholds were abnormal (hyperalgesia) in diabetic (fa/fa) vs. nondiabetic (+/+) rats, and sub cutaneous infusion of IGF-II restored thresholds toward normal. The lo w dose of IGF-II that prevented hyperalgesia in contrast had no effect on hyperglycemia or obesity. These data suggest that IGF treatment ma y provide rational therapy for diabetic neuropathy and that therapy ma y be effective even in patients unable to adequately control their hyp erglycemia.