Sympathetic nervous system and insulin resistance: From obesity to diabetes

As the world faces an obesity "epidemic." the mechanisms by which overweigh t is translated into insulin resistance, hypertension. and diabetes need to be better understood. Although the processes of transition remain uncertai n, overactivity of the sympathetic nervous system appears pivotal. In obesi ty, there is stimulation of sympathetic outflow to the kidneys, evident in increased rates of spillover of noradrenaline into the renal veins, and to skeletal muscle vasculature, demonstrated with microneurography. The cause is unclear, but possibly involves the stimulatory action of leptin released from adipose tissue, or from within the brain. for which there is recent e vidence in human obesity. The high renal sympathetic tone contributes to hy pertension development by stimulating renin secretion and through promoting renal tubular reabsorption of sodium. Neurally mediated skeletal muscle va soconstriction reduces glucose delivery and uptake in muscle. Impairment of glucose uptake by skeletal muscle is a hallmark of insulin resistance synd romes. Pharmacologic sympathetic nervous suppression within the central ner vous system with imidazoline receptor-binding agents such as rilmenidine is a logical therapeutic approach for lowering blood pressure (BP) in patient s with essential hypertension, in whom sympathetic activity is often increa sed. In addition, drugs of this class appear to have the capacity to favora bly modify insulin sensitivity, which has particular relevance in the treat ment of hypertensive diabetic patients. In the hypertension accompanying ma turity onset obesity, with recent recommendations from advisory bodies sett ing lower goal BP, and with these lower targets often being reached only wi th combinations of antihypertensive agents, it is advisable that all drugs used in combination therapy have a favorable or at least a neutral effect o n insulin resistance. (C) 2001 American Journal of Hypertension, Ltd.