TY - JOUR
T1 - Contribution of muscle and liver to glucose-fatty acid cycle in humans
AU - Saloranta, C.
AU - Koivisto, V.
AU - Widen, E.
AU - Falholt, K.
AU - DeFronzo, R. A.
AU - Harkonen, M.
AU - Groop, L. C.
PY - 1993
Y1 - 1993
N2 - To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin. Suppression of HGP by insulin was impaired by elevated plasma FFA levels. Furthermore, the increase in plasma FFA was associated with a 20% reduction in total glucose metabolism (P < 0.01), which was completely accounted for by a reduction in the rate of glucose oxidation. Although the fractional activity of GS was increased by insulin, elevation of plasma FFA had no influence on this key enzyme of glycogen synthesis. In addition, the activities of PDH and CPT were uninfluenced by the elevation of FFA, suggesting that oxidative processes in skeletal muscle were not a major target for the operative glucose-fatty acid cycle under the current conditions. Taken together, the data indicate that the interaction between FFA and glucose metabolism also involves impaired suppression of HGP by insulin.
AB - To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin. Suppression of HGP by insulin was impaired by elevated plasma FFA levels. Furthermore, the increase in plasma FFA was associated with a 20% reduction in total glucose metabolism (P < 0.01), which was completely accounted for by a reduction in the rate of glucose oxidation. Although the fractional activity of GS was increased by insulin, elevation of plasma FFA had no influence on this key enzyme of glycogen synthesis. In addition, the activities of PDH and CPT were uninfluenced by the elevation of FFA, suggesting that oxidative processes in skeletal muscle were not a major target for the operative glucose-fatty acid cycle under the current conditions. Taken together, the data indicate that the interaction between FFA and glucose metabolism also involves impaired suppression of HGP by insulin.
KW - carnitine palmitoyltransferase
KW - free fatty acids
KW - glycogen synthase
KW - hepatic glucose production
KW - pyruvate dehydrogenase
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U2 - 10.1152/ajpendo.1993.264.4.e599
DO - 10.1152/ajpendo.1993.264.4.e599
M3 - Article
C2 - 8476039
AN - SCOPUS:0027475061
SN - 0002-9513
VL - 264
SP - E599-E605
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 4 27-4
ER -