We are interested in the molecular mechanism by which the insulin-like growth factor (IGF) hormones contribute to the development of the nervous system, and to nerve regeneration. Also, we are studying the cause of diabetic neuropathy. This laboratory found that IGFs have neurotrophic properties. Their genes are expressed in brain and spinal cord, and IGF-II gene expression in perinatal muscle correlates closely with snyaptogenesis in rats. Neurite (axon or dendrite) outgrowth and survival of neurons in culture is supported. Following nerve crush, infusion of IGFs increase, whereas anti-IGF antibodies decrease the rate of sciatic nerve regeneration in rats. IGF-I mRNAs are increased all along the nerve distal to crush, whereas IGF-II mRNAs are increased mostly at the end of nerves. IGFs are the first mammalian genes known to regulate the rate of nerve regeneration.

Nearly 13 million American have diabetes, and approximately 10% have symptomatic neuropathy including unrelenting pain, bladder dysfunction, impotence, muscle weakness, and gastroparesis. About 50,000 diabetic limb amputations are performed each year. It is proposed that abnormally low IGF activity in diabetes may be pathogenic for neuropathy. Diabetic rats were found to have reduced IGF gene expression in liver, spinal cord, and nerves. Moreover, treatment with IGFs prevented neuropathy, despite unabated hyperglycemia. Because type I (juvenile) and type II (adult onset) diabetic patients have reduced circulating IGF levels, these studies suggest that IGF might be used to treat patients, but clinical trials are required.

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Pulford BE and Ishii DN (2001) Uptake of Circulating Insulin-Like Growth Factors (IGFs) into Cerebrospinal Fluid Appears to Be Independent of the IGF Receptors as Well as IGF-Binding Proteins. Endocrinology 142: 213-220.