scholarly journals Glucose metabolism in perfused skeletal muscle. Pyruvate dehydrogenase activity in starvation, diabetes and exercise

1976 ◽  
Vol 158 (2) ◽  
pp. 203-210 ◽  
Author(s):  
S A Hagg ◽  
S I Taylor ◽  
N B Ruberman
Keyword(s):  
Skeletal Muscle ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Preceding Paper ◽  
Diabetic Rats ◽  
Pyruvate Dehydrogenase Kinase ◽  
Lactate Oxidation ◽  
Pyruvate Oxidation ◽  
Measured Activity ◽  
Exercise Induced

1. The interconversion of pyruvate dehydrogenase between its inactive phosphorylated and active dephosphorylated forms was studied in skeletal muscle. 2. Exercise, induced by electrical stimulation of the sciatic nerve (5/s), increased the measured activity of (active) pyruvate dehydrogenase threefold in intact anaesthetized rated within 2 min. No further increase was seen after 15 min of stimulation. 3. In the perfused rat hindquarter, (active) pyruvate dehydrogenase activity was decreased by 50% in muscle of starved and diabetic rats. Exercise produced a twofold increase in its activity in all groups; however, the relative differences between fed, starved and diabetic groups persisted. 4. Perfusion of muslce with acetoacetate (2 mM) decreased (active) pyruvate dehydrogenase activity by 50% at rest but not during exercise. 5. Whole-tissue concentrations of pyruvate and citrate, inhibitors of (active) pyruvate dehydrogenase kinase and (inactive) pyruvate dehydrogenase phosphate phosphatase respectively, were not altered by excerise. A decrease in the ATP/ADP ratio was observed, but did not appear to be sufficient to account for the increase in (active) pyruvate dehydrogenase activity. 6. The results suggest that interconversion of the phosphorylated and dephosphorylated forms of pyruvate dehydrogenase plays a major role in the regulation of pyruvate oxidation by eomparison of enzyme activity with measurements of lactate oxidation in the perfused hindquarter [see the preceding paper, Berger et al. (1976)] suggest that pyruvate oxidation is also modulated by the concentrations of substrates, cofactors and inhibitors of (active) pyruvate dehydrogenase activity.

Lactate Production and Pyruvate Dehydrogenase Activity in Fat and Skeletal Muscle From Diabetic Rats

Diabetes ◽  
1992 ◽  
Vol 41 (12) ◽  
pp. 1547-1554 ◽  
Author(s):  
C. E. Mondon ◽  
I. R. Jones ◽  
S. Azhar ◽  
C. B. Hollenbeck ◽  
G. M. Reaven
Keyword(s):  
Skeletal Muscle ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Lactate Production ◽  
Diabetic Rats

Lactate production and pyruvate dehydrogenase activity in fat and skeletal muscle from diabetic rats

Diabetes ◽  
1992 ◽  
Vol 41 (12) ◽  
pp. 1547-1554 ◽  
Author(s):  
C. E. Mondon ◽  
I. R. Jones ◽  
S. Azhar ◽  
C. B. Hollenbeck ◽  
G. M. Reaven
Keyword(s):  
Skeletal Muscle ◽  
Dehydrogenase Activity ◽  
Pyruvate Dehydrogenase ◽  
Lactate Production ◽  
Diabetic Rats

scholarly journals Fibre-type specific modification of the activity and regulation of skeletal muscle pyruvate dehydrogenase kinase (PDK) by prolonged starvation and refeeding is associated with targeted regulation of PDK isoenzyme 4 expression

2000 ◽  
Vol 346 (3) ◽  
pp. 651-657 ◽  
Author(s):  
Mary C. SUGDEN ◽  
Alexandra KRAUS ◽  
Robert A. HARRIS ◽  
Mark J. HOLNESS
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Pyruvate Dehydrogenase ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Cycle ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Anterior Tibialis

Using immunoblot analysis with antibodies raised against recombinant pyruvate dehydrogenase kinase (PDK) isoenzymes PDK2 and PDK4, we demonstrate selective changes in PDK isoenzyme expression in slow-twitch versus fast-twitch skeletal muscle types in response to prolonged (48 h) starvation and refeeding after starvation. Starvation increased PDK activity in both slow-twitch (soleus) and fast-twitch (anterior tibialis) skeletal muscle and was associated with loss of sensitivity of PDK to inhibition by pyruvate, with a greater effect in anterior tibialis. Starvation significantly increased PDK4 protein expression in both soleus and anterior tibialis, with a greater response in anterior tibialis. Starvation did not effect PDK2 protein expression in soleus, but modestly increased PDK2 expression in anterior tibialis. Refeeding for 4 h partially reversed the effect of 48-h starvation on PDK activity and PDK4 expression in both soleus and anterior tibialis, but the response was more marked in soleus than in anterior tibialis. Pyruvate sensitivity of PDK activity was also partially restored by refeeding, again with the greater response in soleus. It is concluded that targeted regulation of PDK4 isoenzyme expression in skeletal muscle in response to starvation and refeeding underlies the modulation of the regulatory characteristics of PDK in vivo. We propose that switching from a pyruvate-sensitive to a pyruvate-insensitive PDK isoenzyme in starvation (a) maintains a sufficiently high pyruvate concentration to ensure that the glucose → alanine → glucose cycle is not impaired, and (b) may ‘spare’ pyruvate for anaplerotic entry into the tricarboxylic acid cycle to support the entry of acetyl-CoA derived from fatty acid (FA) oxidation into the tricarboxylic acid cycle. We further speculate that FA oxidation by skeletal muscle is both forced and facilitated by upregulation of PDK4, which is perceived as an essential component of the operation of the glucose-FA cycle in starvation.

scholarly journals Increased pyruvate dehydrogenase activity in skeletal muscle of growth-restricted ovine fetuses

2019 ◽  
Vol 317 (4) ◽  
pp. R513-R520 ◽  
Author(s):  
Alexander L. Pendleton ◽  
Laurel R. Humphreys ◽  
Melissa A. Davis ◽  
Leticia E. Camacho ◽  
Miranda J. Anderson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Intrauterine Growth Restriction ◽  
Citrate Synthase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Semitendinosus Muscle ◽  
Fetal Sheep ◽  
Pyruvate Dehydrogenase Phosphatase ◽  
And Control ◽  
Fetal Muscle

Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower fractional rates of glucose oxidation and greater gluconeogenesis, indicating lactate shuttling between skeletal muscle and liver. Suppression of pyruvate dehydrogenase ( PDH) activity was proposed because of greater pyruvate dehydrogenase kinase (PDK) 4 and PDK1 mRNA concentrations in IUGR muscle. Although PDK1 and PDK4 inhibit PDH activity to reduce pyruvate metabolism, PDH protein concentrations and activity have not been examined in skeletal muscle from IUGR fetuses. Therefore, we evaluated the protein concentrations and activity of PDH and the kinases and phosphatases that regulate PDH phosphorylation status in the semitendinosus muscle from placenta insufficiency-induced IUGR sheep fetuses and control fetuses. Immunoblots were performed for PDH, phosphorylated PDH (E1α), PDK1, PDK4, and pyruvate dehydrogenase phosphatase 1 and 2 (PDP1 and PDP2, respectively). Additionally, the PDH, lactate dehydrogenase (LDH), and citrate synthase (CS) enzymatic activities were measured. Phosphorylated PDH concentrations were 28% lower (P < 0.01) and PDH activity was 67% greater (P < 0.01) in IUGR fetal muscle compared with control. PDK1, PDK4, PDP1, PDP2, and PDH concentrations were not different between groups. CS and LDH activities were also unaffected. Contrary to the previous speculation, PDH activity was greater in skeletal muscle from IUGR fetuses, which parallels lower phosphorylated PDH. Therefore, greater expression of PDK1 and PDK4 mRNA did not translate to greater PDK1 or PDK4 protein concentrations or inhibition of PDH as proposed. Instead, these findings show greater PDH activity in IUGR fetal muscle, which indicates that alternative regulatory mechanisms are responsible for lower pyruvate catabolism.

Inverse alterations of BCKA dehydrogenase activity in cardiac and skeletal muscles of diabetic rats

1999 ◽  
Vol 277 (4) ◽  
pp. E685-E692 ◽  
Author(s):  
Yolanda B. Lombardo ◽  
Cynthia Serdikoff ◽  
Manikkavasagar Thamotharan ◽  
Harbhajan S. Paul ◽  
Siamak A. Adibi
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Protein Expression ◽  
Cardiac Muscle ◽  
Dehydrogenase Activity ◽  
Skeletal Muscles ◽  
Diabetic Rats ◽  
Gene Expressions ◽  
The Difference ◽  
Activity State

Rat cardiac and skeletal muscles, which have been used as model tissues for studies of regulation of branched-chain α-keto acid (BCKA) oxidation, vary greatly in the activity state of their BCKA dehydrogenase. In the present experiment, we have investigated whether they also vary in response of their BCKA dehydrogenase to a metabolic alteration such as diabetes and, if so, to investigate the mechanism that underlies the difference. Diabetes was produced by depriving streptozotocin-treated rats of insulin administration for 96 h. The investigation of BCKA dehydrogenase in the skeletal muscle (gastrocnemius) showed that diabetes 1) increased its activity, 2) increased the protein and gene expressions of all of its subunits (E1α, E1β, E2), 3) increased its activity state, 4) decreased the rate of its inactivation, and 5) decreased the protein expression of its associated kinase (BCKAD kinase) without affecting its gene expression. In sharp contrast, the investigation of BCKA dehydrogenase in the cardiac muscle showed that diabetes 1) decreased its activity, 2) had no effect on either protein or gene expression of any of its subunits, 3) decreased its activity state, 4) increased its rate of inactivation, and 5) increased both the protein and gene expressions of its associated kinase. In conclusion, our data suggest that, in diabetes, the protein expression of BCKAD kinase is downregulated posttranscriptionally in the skeletal muscle, whereas it is upregulated pretranslationally in the cardiac muscle, causing inverse alterations of BCKA dehydrogenase activity in these muscles.

scholarly journals Effects of aerobic training on pyruvate dehydrogenase and pyruvate dehydrogenase kinase in human skeletal muscle

2004 ◽  
Vol 557 (2) ◽  
pp. 559-570 ◽  
Author(s):  
Paul J. LeBlanc ◽  
Sandra J. Peters ◽  
Rebecca J. Tunstall ◽  
David Cameron-Smith ◽  
George J. F. Heigenhauser
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Aerobic Training ◽  
Pyruvate Dehydrogenase Kinase

Increased pyruvate dehydrogenase kinase activity in response to sepsis

1991 ◽  
Vol 260 (5) ◽  
pp. E669-E674 ◽  
Author(s):  
T. C. Vary
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Kinase Activity ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Dehydrogenase Kinase ◽  
Sterile Inflammation ◽  
Stable Factor ◽  
Skeletal Muscle Mitochondria ◽  
Dependent Inactivation ◽  
Significant Difference

The effect of sterile inflammation and sepsis on the proportion of active pyruvate dehydrogenase complex (PDH) in mitochondria isolated from skeletal muscle has been investigated. The proportion of active PDH in mitochondria isolated from septic animals was significantly reduced compared with control under all incubation conditions examined, even in the presence of inhibitors of the PDH kinase. There was no significant difference between control and sterile inflammation in any of the incubations examined. The rate constant for ATP-dependent inactivation of the PDH complex in mitochondrial extracts from control animals was -0.42 min-1 (r = 0.993; P less than 0.001) and was not altered in mitochondrial extracts from sterile inflammatory animals (-0.43 min-1; r = 0.999; P less than 0.001). However, rate constants for inactivation in septic animals was significantly increased over twofold to -1.08 min-1 (r = 0.987; P less than 0.001) (P less than 0.001 vs. control or sterile inflammation). In the presence of inhibitors of the PDH kinase reaction (2.5 mM pyruvate or 1 mM dichloroacetate), inactivation of PDH after addition of ATP was significantly greater in mitochondrial extracts from septic than either control or sterile inflammatory animals. These results suggest that sepsis, but not sterile inflammation, induces a stable factor in skeletal muscle mitochondria that increased PDH kinase activity.

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