Metabolism: clinical and experimental
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An alcoholic extract of Artemisia dracunculus L (PMI 5011) has been shown to decrease glucose and improve insulin levels in animal models, suggesting an ability to enhance insulin sensitivity. We sought to assess the cellular mechanism by which this botanical affects carbohydrate metabolism in primary human skeletal muscle culture. We measured basal and insulin-stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skeletal muscle culture from subjects with type 2 diabetes mellitus incubated with or without various concentrations of PMI 5011. ⋯ However, PMI 5011 significantly decreased levels of a specific protein tyrosine phosphatase, that is, PTP1B. Time course studies confirmed that protein abundance of PTP1B decreases in the presence of PMI 5011. The cellular mechanism of action to explain the effects by which an alcoholic extract of A dracunculus L improves carbohydrate metabolism on a clinical level may be secondary to enhancing insulin receptor signaling and modulating levels of a specific protein tyrosine phosphatase, that is, PTP1B.
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Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is considered to play a pivotal role in the exercise-induced metabolic adaptation of skeletal muscle. Although the oxidized form of nicotinamide adenine dinucloetide (NAD(+))-dependent histone deacetylase SIRT1 has been shown to mediate PGC-1alpha-induced metabolic adaptation, the effect of endurance exercise on the SIRT1 protein remains to be elucidated. The purposes of this study were (1) to investigate the distribution of SIRT1 and PGC-1alpha proteins in skeletal muscle and (2) to examine the effects of acute endurance exercise and low- or high-intensity exercise training on SIRT1 and PGC-1alpha protein expressions and on the metabolic components in rat skeletal muscle. ⋯ In the plantaris muscle, SIRT1, hexokinase activity, mitochondrial proteins and enzyme activities, and glucose transporter 4 were increased by high-intensity training whereas the PGC-1alpha was not. These results suggest that endurance exercise increases the skeletal muscle SIRT1 protein content. In addition, the findings also raise the possibility that the SIRT1 protein expression may play a potentially important role in such adaptations, whereas an increase in the PGC-1alpha protein expression is not necessary for such adaptations.