Author(s): Ishii DN
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Abstract Neuropathy can be a highly debilitating complication for about 10-15\% of diabetic individuals. Unfortunately, the complex syndrome has proven difficult to explain and a consensus as to its cause has not emerged. It has recently come to light that insulin and insulin-like growth factors (IGFs) have neurotrophic actions on sensory, sympathetic and motor neurons. These are the main types of neurons afflicted in this disorder. Moreover, IGF activity is reduced in both clinical and experimental diabetes. The premise that insulin, IGF-I and IGF-II provide redundant neurotrophic support underlies the following new theory for pathogenesis of diabetic neural disturbances: a loss of insulin activity leads to a secondary partial decline in IGF-I activity. Although most of the redundant neurotrophic support is thereby eliminated, IGF-II activity continues to support the nervous system. The final enemy is time and the relentless age- and duration-dependent run-down of IGF activity is suggested to contribute to the age- and duration-dependent neuropathy. Weight loss or anorexia nervosa are independent risk factors that can cause a rapid, painful neuropathy to develop as a result of a rapid loss of IGF activity. A distinguishing feature of this new theory is that hyperglycemia is not considered to be the main culprit. The following critical predictions from the theory were tested in diabetic rats: (i) IGF activity is reduced in diabetic neural tissues; (ii) conduction velocity is impaired in the diabetic spinal cord; (iii) replacement therapy with IGF can prevent neuropathy in diabetic nerves; and (iv) IGFs can prevent diabetic neuropathy, despite hyperglycemia. All of these predictions have been validated. It is hoped that a fresh perspective will stimulate renewed study into the causation of this most unfortunate disorder.
This article was published in Brain Res Brain Res Rev
and referenced in Journal of Diabetes & Metabolism