The Relation between Insulin Sensitivity and the Fatty-Acid Composition of Skeletal-Muscle Phospholipids

Abstract

Background: Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. Methods: We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. Results: In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P<0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = -0.68, P<0.001); the average degree of fatty-acid unsaturation (r = -0.61, P<0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = -0.55, P<0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = 0.76, P<0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = 0.76, P<0.01), the average degree of fatty-acid unsaturation (r = 0.62, P<0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = 0.78, P = 0.007). Conclusions: Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin., Hyperinsulinemia, which reflects the impaired sensitivity of tissue to the action of insulin (insulin resistance), is a risk factor for several common disorders1,2. Insulin resistance is a characteristic finding in patients with non-insulin-dependent diabetes mellitus, is common in persons at increased risk for this type of diabetes,3 and also occurs in persons with normal glucose tolerance,4 frequently in association with obesity,2 hypertension,5 hyperlipidemia,6 and coronary artery disease1,2. It has been postulated that insulin resistance, through compensatory hyperinsulinemia, has a pathogenic role in the development of these disorders1,7. Skeletal muscle is the principal site of… © 1993, Massachusetts Medical Society. All rights reserved.