OBJECTIVEWe have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance.RESEARCH DESIGN AND METHODSInsulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg−1 · min−1).RESULTSIntralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men (P < 0.05), and insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by intralipid.CONCLUSIONSIntralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.

Rose AJ, Bisiani B, Vistisen B, Kiens B, Richter EA. Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type. Am J Physiol Regul Integr Comp Physiol 296: R326 -R333, 2009. First published November 26, 2008 doi:10.1152/ajpregu.90806.2008.-Protein synthesis in skeletal muscle is known to decrease during exercise, and it has been suggested that this may depend on the magnitude of the relative metabolic stress within the contracting muscle. To examine the mechanisms behind this, the effect of exercise intensity on skeletal muscle eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) phosphorylation, key components in the mRNA translation machinery, were examined together with AMP-activated protein kinase (AMPK) in healthy young men. Skeletal muscle eEF2 phosphorylation at Thr 56 increased during exercise but was not influenced by exercise intensity, and was lower than rest 30 min after exercise. On the other hand, 4EBP1 phosphorylation at Thr 37/46 decreased during exercise, and this decrease was greater at higher exercise intensities and was similar to rest 30 min after exercise. AMPK activity, as indexed by AMPK ␣-subunit phosphorylation at Thr 172 and phosphorylation of the AMPK substrate ACC␤ at Ser 221 , was higher with higher exercise intensities, and these indices were higher than rest after high-intensity exercise only. Using immunohistochemistry, it was shown that the increase in skeletal muscle eEF2 Thr 56 phosphorylation was restricted to type I myofibers. Taken together, these data suggest that the depression of skeletal muscle protein synthesis with endurance-type exercise may be regulated at both initiation (i.e., 4EBP1) and elongation (i.e., eEF2) steps, with eEF2 phosphorylation contributing at all exercise intensities but 4EBP1 dephosphorylation contributing to a greater extent at high vs. low exercise intensities. protein synthesis; translation; elongation; initiation; AMPK IT IS RECOGNIZED THAT THE understanding of the mechanisms controlling skeletal muscle protein turnover may aid in the development of novel therapies to combat skeletal muscle diseases (30). The control of protein turnover in skeletal muscle during exercise is poorly understood (30). It is known that skeletal muscle protein synthesis is blunted during exercise (2, 13). A recent study (24) demonstrated that contractile activity was a potent stimulus to blunt net protein synthesis rate of rat skeletal muscle ex vivo and can even override the anabolic effect of insulin. Studies by BylundFellenius et al. (7) in perfused rat hindquarters demonstrated that protein synthesis rates were lower in contracting compared with resting skeletal muscle, particularly in fast-twitch muscles. In that study (7), it was shown that the magnitude of the blunting of protein synthesis was related to the magnitude of changes in high-energy phosphogens, indicating that signaling downstream of metabolic stress is a likely mechanism behind the fall...