Skeletal muscle lactate overproduction during metformin intoxication: An animal study with reverse microdialysis

It has been suggested that during a skeletal muscle contraction the metabolic energy cost at the onset may be greater than the energy cost related to holding steady-state force. The purpose of the present study was to investigate the effect of contraction duration on the metabolic energy cost and fatigue process in fully perfused contracting muscle in situ. Canine gastrocnemius muscle ( n = 6) was isolated, and two contractile periods (3 min of isometric, tetanic contractions with 45-min rest between) were conducted by each muscle in a balanced order design. The two contractile periods had stimulation patterns that resulted in a 1:3 contraction-to-rest ratio, with the difference in the two contractile periods being in the duration of each contraction: short duration 0.25-s stimulation/0.75-s rest vs. long duration 1-s stimulation/3-s rest. These stimulation patterns resulted in the same total time of stimulation, number of stimulation pulses, and total time in contraction for each 3-min period. Muscle O2 uptake, the fall in developed force (fatigue), the O2 cost of developed force, and the estimated total energy cost (ATP utilization) of developed force were significantly greater ( P < 0.05) with contractions of short duration. Lactate efflux from the working muscle and muscle lactate concentration were significantly greater with contractions of short duration, such that the calculated energy derived from glycolysis was three times greater in this condition. These results demonstrate that contraction duration can significantly affect both the aerobic and anaerobic metabolic energy cost and fatigue in contracting muscle. In addition, it is likely that the greater rate of fatigue with more rapid contractions was a result of elevated glycolytic production of lactic acid.

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Carbohydrate ingestion does not alter skeletal muscle AMPK signaling during exercise in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00023.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. E566-E573 ◽

Cited By ~ 26

Author(s):

Robert S. Lee-Young ◽

Matthew J. Palmer ◽

Kelly C. Linden ◽

Kieran LePlastrier ◽

Benedict J. Canny ◽

...

Keyword(s):

Skeletal Muscle ◽

Plasma Glucose ◽

Plasma Epinephrine ◽

Muscle Lactate ◽

Carbohydrate Ingestion ◽

Ampk Signaling ◽

Glucose Levels ◽

Exercise Induced ◽

Exercise In Humans

There is evidence that increasing carbohydrate (CHO) availability during exercise by raising preexercise muscle glycogen levels attenuates the activation of AMPKα2 during exercise in humans. Similarly, increasing glucose levels decreases AMPKα2 activity in rat skeletal muscle in vitro. We examined the effect of CHO ingestion on skeletal muscle AMPK signaling during exercise in nine active male subjects who completed two 120-min bouts of cycling exercise at 65 ± 1% V̇o2 peak. In a randomized, counterbalanced order, subjects ingested either an 8% CHO solution or a placebo solution during exercise. Compared with the placebo trial, CHO ingestion significantly ( P < 0.05) increased plasma glucose levels and tracer-determined glucose disappearance. Exercise-induced increases in muscle-calculated free AMP (17.7- vs. 11.8-fold), muscle lactate (3.3- vs. 1.8-fold), and plasma epinephrine were reduced by CHO ingestion. However, the exercise-induced increases in skeletal muscle AMPKα2 activity, AMPKα2 Thr172 phosphorylation and acetyl-CoA Ser222 phosphorylation, were essentially identical in the two trials. These findings indicate that AMPK activation in skeletal muscle during exercise in humans is not sensitive to changes in plasma glucose levels in the normal range. Furthermore, the rise in plasma epinephrine levels in response to exercise was greatly suppressed by CHO ingestion without altering AMPK signaling, raising the possibility that epinephrine does not directly control AMPK activity during muscle contraction under these conditions in vivo.

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Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.3.e458 ◽

1995 ◽

Vol 269 (3) ◽

pp. E458-E468 ◽

Cited By ~ 29

Author(s):

C. T. Putman ◽

N. L. Jones ◽

L. C. Lands ◽

T. M. Bragg ◽

M. G. Hollidge-Horvat ◽

...

Keyword(s):

Skeletal Muscle ◽

Pyruvate Dehydrogenase ◽

Maximal Exercise ◽

Vastus Lateralis ◽

Active Form ◽

Lactate Production ◽

Glycolytic Flux ◽

Muscle Lactate ◽

Mitochondrial Oxidation ◽

Exercise In Humans

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.

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Extracellular hyper‐osmolality increases resting skeletal muscle lactate in mammalian skeletal muscle

The FASEB Journal ◽

10.1096/fasebj.20.4.a816-a ◽

2006 ◽

Vol 20 (4) ◽

Author(s):

Brian D. Roy ◽

Sandra J. Peters ◽

Paul J. Leblanc ◽

AnaMarie Antolic

Keyword(s):

Skeletal Muscle ◽

Mammalian Skeletal Muscle ◽

Muscle Lactate

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Phosphorylase a in human skeletal muscle during exercise and electrical stimulation

Journal of Applied Physiology ◽

10.1152/jappl.1978.45.6.852 ◽

1978 ◽

Vol 45 (6) ◽

pp. 852-857 ◽

Cited By ~ 8

Author(s):

P. D. Gollnick ◽

J. Karlsson ◽

K. Piehl ◽

B. Saltin

Keyword(s):

Skeletal Muscle ◽

Electrical Stimulation ◽

Human Skeletal Muscle ◽

Vastus Lateralis ◽

Muscular Activity ◽

Voluntary Exercise ◽

Vastus Lateralis Muscle ◽

Minor Importance ◽

Muscle Lactate ◽

Needle Technique

Experiments were conducted to examine the conversions of phosphorylase b to phosphorylase a in human skeletal muscle during bicycle exercise or isometric contractions. Muscle biopsies were obtained from the vastus lateralis with the needle technique at rest and either during or immediately after activity and frozen in liquid nitrogen within 2--4 s. Total phosphorylase and phosphorylase a activities were differentiated by measurement in the presence and absence of AMP, respectively. At rest 8.5% of the total phosphorylase activity existed in the a form. Little or no change in the percent of phosphorylase in the a form occurred during voluntary dynamic or static muscular activity that produced muscle lactate concentrations in excess of 18 mmol.kg-1 wet muscle. Electrical stimulation of the vastus lateralis muscle also failed to produce an increase in the percentage of phosphorylase a. These data suggest that during exercise the conversion of phosphorylase to the a form is of minor importance. An increased activity of phosphorylase b due to changes in muscle concentrations of ATP, AMP, and inorganic phosphate may regulate glycogenolysis during voluntary exercise in man.

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Metabolic changes in skeletal muscle and blood of greyhounds during 800-m track sprint

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.3.r513 ◽

1988 ◽

Vol 255 (3) ◽

pp. R513-R519 ◽

Cited By ~ 3

Author(s):

G. P. Dobson ◽

W. S. Parkhouse ◽

J. M. Weber ◽

E. Stuttard ◽

J. Harman ◽

...

Keyword(s):

Skeletal Muscle ◽

Vastus Lateralis ◽

Fold Increase ◽

Biceps Femoris ◽

Muscle Lactate ◽

Muscle Ph ◽

The Mean ◽

Metabolic Properties ◽

Fast Twitch ◽

Anaerobic Conversion

The aim of this study was to examine some metabolic properties and changes that occur in skeletal muscle and blood of greyhounds after an 800-m sprint. Three prime moving fast-twitch muscles were selected: biceps femoris (BF), gastrocnemius (G), and vastus lateralis (VL). The amount of glycogen utilized during the event was 42.57, 43.86, and 42.73 mumol glucosyl units/g wet wt, respectively. Expressed as a function of race time (48.3 +/- 0.7 s, n = 3), the mean rate of glycogen breakdown was 53.48 +/- 0.5 mumol.g wet wt-1.min-1 during the sprint. This is equivalent to an ATP turnover of 160 mumol.g wet wt-1.min-1, assuming 100% anaerobic conversion to lactate. This represents a conservative estimate, since greyhound muscle is heterogeneous and comprised of a large percentage of fast-twitch oxidative fibers (Armstrong et al., Am. J. Anat. 163: 87-98, 1982). The large decrease in muscle glycogen was accompanied by a 6- to 7-fold increase in muscle lactate from 3.48 +/- 0.13 to 25.42 +/- 3.54 (BF), 2.54 +/- 1.05 to 18.96 +/- 2.60 (G), and 4.57 +/- 0.44 to 30.09 +/- 1.94 mumol.g wet wt (VL), and a fall in muscle pH from 6.88 +/- 0.03 to 6.40 +/- 0.02 (BF), 6.92 +/- 0.02 to 6.56 +/- 0.02 (G), and 6.93 +/- 0.02 to 6.47 +/- 0.01 (VL). Cytosolic phosphorylation potential in BF decreased 10-fold from 11,360 +/- 680 to 1,184 +/- 347, and redox potential decreased 5-fold, indicating a marked reduction in the cytosol at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of Early Severe Malnutrition on Heart and Skeletal Muscle Lactate Dehydrogenase

Journal of Nutrition ◽

10.1093/jn/106.9.1235 ◽

1976 ◽

Vol 106 (9) ◽

pp. 1235-1240 ◽

Cited By ~ 2

Author(s):

David Penney ◽

Debra Anderson ◽

John Dongas

Keyword(s):

Skeletal Muscle ◽

Lactate Dehydrogenase ◽

Severe Malnutrition ◽

Muscle Lactate

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