Altered Nerve Myo-Inositol Metabolism in Experimental Diabetes and Its Relationship to Nerve Function
The following picture of altered myo-inositol metabolism in diabetic peripheral nerve has recently emerged. Hyperglycemia, through competitive inhibition of sodium-dependent myo-inositol uptake and/or increased polyol (sorbitol) pathway activity, reduces nerve myo-inositol content, secondarily altering nerve phosphoinositide metabolism and impairing the function of the membrane-bound sodium-potassium ATPase. The resulting reduction in the transmembrane sodium gradient impairs nerve conduction and further reduces sodium gradient-dependent myo-inositol uptake, creating a self-reinforcing metabolic defect in diabetic peripheral nerve. Other sodium-gradient dependent processes such as amino acid uptake and intracellular water and electrolyte homeostasis may also be secondarily altered. These abnormalities may have potentially widespread pathophysiological implications, possibly leading to the later structural defects in diabetic peripheral nerve, which are thought to underlie neurological deficits in diabetic neuropathy.
KeywordsDiabetic Neuropathy Experimental Diabetes Aldose Reductase Inhibitor Motor Nerve Conduction Velocity Diabetic Nerve
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