Effect of vasodilation on the response of muscle protein synthesis to insulin in aging

Abstract

The loss of muscle with aging (sarcopenia) is an important contributor to disability and physical dependence in older people. Studies have recently found that aging is associated with a relative resistance of muscle proteins to the anabolic action of insulin, even in subjects who do not have diabetes. This alteration impairs the response of older muscle to the anabolic action of a mixed meal, and may contribute to muscle loss with aging. \r\nThe hypothesis is that aging reduces the vascular sensitivity to insulin, which prevents the physiological increase in blood flow and muscle perfusion in response to exogenous or endogenous insulin, thereby decreasing the response of muscle protein synthesis and net balance to the anabolic action of insulin. This study looked at whether the response of muscle protein synthesis and net balance to insulin improves in older subjects when blood flow and muscle perfusion are pharmacologically restored to youthful values. \r\nSix elderly subjects were assigned to a control group which received an insulin infusion in one leg during the intervention period. Another six subjects in the experimental group received insulin as well as the vasodilator, sodium nitroprusside (SNP). Blood flow increased significantly (P<0.001) with the addition of SNP. Using stable isotope methodologies, it was determined that there were also increases in muscle protein anabolism with the addition of SNP. The muscle protein synthesis (mTOR-associated) cell signaling pathways also showed increased phosphorylation of specific insulin-related proteins when vasodilation was increased with SNP.\r\nTherefore, this study showed that pharmacologically restoring blood flow and nutrient delivery to youthful values, did improve the response of muscle protein synthesis to insulin in older subjects. Decreases in blood flow and muscle perfusion are clearly important contributors to the insulin resistance of skeletal muscle in aging. Understanding the mechanisms behind the loss of muscle with aging will serve as a basis for developing effective treatments for sarcopenia in older individuals.