Intramuscular TFGA are 2-4 fold greater in insulin resistant, obese than in lean, insulin sensitive humans. These enlarged lipid stores are proposed to contribute to skeletal muscle insulin resistance vi the glucose fatty acid cycle. Endurance trained humans also have increased intramuscular TGFA, however, and are not insulin resistant. If intramusclar FA contibute to insulin resistance, intramuscular TGFA kinetics must be regulated quite differently in these two groups. The differences could be present under basal conditions in response to insulin or both. We anticipate that basal intramuscular TGFA hydrolysis will be increased in visceral obesity in proportion to the increased TGFA stores, and that hydrolysis rates will not be inhibited by insulin in this group. The results will provide the first available information regarding the kinetics of intramuscular FA in humans and will help us to understand the role of this small, but potentially important lipid pool in the syndrome of insulin resistance/visceral obesity. Early analysis of samples obtained from the first few studies revealed inadequate stable isotope incorporation into the muscle biopsy specimens. Therefore, a protocol change was made increasing the doses of the stable fatty acids and adding radioisotopes of the same fatty acids. To offset the increase in radiation exposure, the 3H-glucose was changed to stable 2H-glucose (IRB and radiation safety approval 10/2 and 9/29 respectively).
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