Fig. 1Metabolic inflexibility in type 2 diabetes.
Fig. 2Energy expenditure and fuel selection during cycling exercise at 75% of VO2max. Adapted from van Loon et al. J Physiol 2001;536(Pt 1):295-304 [1]. FFA, free fatty acid.
Fig. 3Physiological factors that control muscle pyruvate dehydrogenase activity. NAD, nicotinamide adenine dinucleotide; CoASH, coenzyme A; NADH, nicotinamide adenine dinucleotide hydrogen; ATP, adenosine triphosphate; ADP, adenosine diphosphate.
Fig. 4The competition between pyruvate dehydrogenase complex (PDC) activity-mediated carbohydrate oxidation and fat oxidation for the cellular coenzyme A (CoASH) and carnitine availability. NAD, nicotinamide adenine dinucleotide; NADH, nicotinamide adenine dinucleotide hydrogen; ATP, adenosine triphosphate; ADP, adenosine diphosphate; CPT, carnitine palmitoyl carnitine; TCA, tricarboxylic acid.
Fig. 5(A) Muscle pyruvate dehydrogenase kinase isoform 4 (PDK4) and (B) pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1) are concomitantly up- and down-regulated, respectively, in a lipopolysaccharide (LPS)-inflammation model compared with their corresponding control (saline). Adapted from Crossland et al. J Physiol 2008;586(Pt 22):5589-600 [33]. HMBS, hydroxymethylbilane synthase. aSignificantly different from control; P<0.05.
Fig. 6Muscle pyruvate dehydrogenase complex (PDC) activity at rest and after 30 minutes of electrically evoked submaximal intensity isometric contraction after 6 days of medication with different doses of peroxisome proliferator-activated receptor (PPAR)-δ agonist GW610742 (0 mg [control; empty bar], 5 mg [grey bar], and 100 mg kg-1 body weight [black bar]). Adapted from Constantin-Teodosiu et al. J Physiol 2009;587(Pt 1): 231-9 [37]. a,bSignificantly different from the corresponding control; P<0.05.
Fig. 7Rat skeletal muscle force during 30 minutes of electrically evoked submaximal intensity isometric contraction after 6 days of medication with different doses of peroxisome proliferator-activated receptor (PPAR)-δ agonist GW610742. Adapted from Constantin-Teodosiu et al. J Physiol 2009;587 (Pt 1):231-9 [37]. aSignificantly different from vehicle; P<0.05.
Fig. 8Mechanism of forkhead class O (FOXO) 1 mediated pyruvate dehydrogenase kinase isoform (PDK) 4 up-regulation and thereby pyruvate dehydrogenase complex (PDC)-mediated inhibition of carbohydrate oxidation. GLUT4, glucose transporter isoform 4; IGF, insulin-like growth factor; FFA, free fatty acid; TNF, tumor necrosis factor; PTEN, phosphatase and tensin homolog; PI3K, phosphoinositol 3-kinase; GSK, glycogen synthase; IRS-1, insulin receptor substrate 1.
Fig. 9Human quadriceps muscle pyruvate dehydrogenase complex activity (PDCa) at rest, 10 and 60 minutes of submaximal intensity exercise (75% VO2max) with dichloroacetate (DCA) or saline infusion prior to exercise after 3 days of either a standard diet (CD) or high-fat diet (HFD). Adapted from Constantin-Teodosiu et al. Diabetes 2012;61:1017-24, with permission from American Diabetes Association [2].
Fig. 10Ways to improve muscle glucose disposal in type 2 diabetes patients. PDC, pyruvate dehydrogenase complex.
Table 1Metabolite levels in human skeletal muscle at rest and after 3×30 minutes bouts of exercise at 40%, 55%, and 75% of VO2max