TY - JOUR
T1 - Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man
AU - Clore, John N.
AU - Harris, Paul A.
AU - Li, Jing
AU - Azzam, Amin
AU - Gill, Ranjodh
AU - Zuelzer, Wilhelm
AU - Rizzo, William B.
AU - Blackard, William G.
N1 - Funding Information:
From the Departments of lnternal Medicine, Surgery, and Pediatrics, Virginia Commonwealth University, Richmond, VA tDeceased. Submitted April 14, 1999; accepted June 8, 1999. Supported in part by National Institutes of Health Grants No. R01 DK43013, R01 DK18903, and M01 RRO0065. Address reprint requests to John N. Clore, MD, Box 980155, Medical College of Virginia/Virghffa Commonwealth University, Richmond, VA 23298. Copyright © 2000 by W.B. Saunders Company 0026-0495/00/4902-0028510.00/0
PY - 2000
Y1 - 2000
N2 - The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic- euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 ± 7.5 to 64.6 ± 9.0 μU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% ± 0.3% to 21.7% ± 0.4%, P < .05) and decreases in 18:0 (6.2% ± 0.5% to 5.1% ± 0.4%, P = .01), long-chain n-3 fatty acids (1.7% ± 0.2% to 1.4% ± 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% ± 0.8% to 8.0% ± 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man. (C) 2000 by W.B. Saunders Company.
AB - The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic- euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 ± 7.5 to 64.6 ± 9.0 μU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% ± 0.3% to 21.7% ± 0.4%, P < .05) and decreases in 18:0 (6.2% ± 0.5% to 5.1% ± 0.4%, P = .01), long-chain n-3 fatty acids (1.7% ± 0.2% to 1.4% ± 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% ± 0.8% to 8.0% ± 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man. (C) 2000 by W.B. Saunders Company.
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U2 - 10.1016/S0026-0495(00)91455-0
DO - 10.1016/S0026-0495(00)91455-0
M3 - Article
C2 - 10690951
AN - SCOPUS:0033960344
SN - 0026-0495
VL - 49
SP - 232
EP - 238
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 2
ER -