Anti-PDK2 (full length) polyclonal antibody

Background. The aim was to investigate the molecular mechanisms behind exercise training-induced improvements in glucose regulation in aged subjects. Methods. Twelve elderly male subjects completed 8 weeks of exercise training. Before and after the training period, the subjects completed an oral glucose tolerance test (OGTT) and a muscle biopsy was obtained from the vastus lateralis before and 45 minutes into the OGTT. Blood samples were collected before and up to 120 minutes after glucose intake. Results. Exercise training increased Hexokinase II, GLUT4, Akt2, glycogen synthase (GS), pyruvate dehydrogenase (PDH)-E1 alpha, PDK2 protein, and glycogen content in skeletal muscle. Furthermore, in response to glucose, GS activity was increased and the dephosphorylation of GS site 2 + 2a and 3a was enhanced after the training intervention. The glucose-mediated insulin stimulation of TBC1D4 Thr642 phosphorylation was increased after exercise training. In the trained state, the PDHa activity was reduced following glucose intake and without changes in phosphorylation level of PDH-E1 alpha. Conclusions. The present results suggest that exercise training improves glucose regulation in elderly subjects by enhancing the capacity and acute regulation of glucose uptake and by enhancing intracellular glucose removal to glycogen synthesis rather than glucose oxidation.

Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1 alpha (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P = 0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained similar to 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1 alpha explained similar to 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1 alpha), in concert with higher potential for PDH activation (PDP activity).