scholarly journals Inhibition of glucose uptake and glycogenolysis by availability of oleate in well-oxygenated perfused skeletal muscle

1977 ◽  
Vol 168 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Michael J. Rennie ◽  
John O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Contractile Activity ◽  
Haemoglobin Concentration ◽  
Lactate Production ◽  
O2 Uptake ◽  
Perfusion Medium ◽  
Red Muscle ◽  
Intracellular Glucose

The effects of exogenous oleate on glucose uptake, lactate production and glycogen concentration in resting and contracting skeletal muscle were studied in the perfused rat hindquarter. In preliminary studies with aged erythrocytes at a haemoglobin concentration of 8g/100ml in the perfusion medium, 1.8mm-oleate had no effect on glucose uptake or lactate production. During these studies it became evident that O2 delivery was inadequate with aged erythrocytes. Perfusion with rejuvenated human erythrocytes at a haemoglobin concentration of 12g/100ml resulted in a 2-fold higher O2 uptake at rest and a 4-fold higher O2 uptake during muscle contraction than was obtained with aged erythrocytes. Rejuvenated erythrocytes were therefore used in subsequent experiments. Glucose uptake and lactate production by the well-oxygenated hindquarter were inhibited by one-third, both at rest and during muscle contraction, when 1.8mm-oleate was added to the perfusion medium. Addition of oleate also significantly protected against glycogen depletion in the fast-twitch red and slow-twitch red types of muscle, but not in white muscle, during sciatic-nerve stimulation. In the absence of added oleate, glucose was confined to the extracellular space in resting muscle. Addition of oleate resulted in intracellular glucose accumulation in red muscle. Contractile activity resulted in accumulation of intracellular glucose in all three muscle types, and this effect was significantly augmented in the red types of muscle by perfusion with oleate. The concentrations of citrate and glucose 6-phosphate were also increased in red muscle perfused with oleate. We conclude that, as in the heart, availability of fatty acids has an inhibitory effect on glucose uptake and glycogen utilization in well-oxygenated red skeletal muscle.

Contractile activity increases glucose uptake by muscle in severely diabetic rats

1984 ◽  
Vol 57 (4) ◽  
pp. 1045-1049 ◽  
Author(s):  
H. Wallberg-Henriksson ◽  
J. O. Holloszy
Keyword(s):  
Muscle Contraction ◽  
Glucose Uptake ◽  
Contractile Activity ◽  
Diabetic Rats ◽  
Perfusion Medium ◽  
Plasma Insulin Levels ◽  
Flow Through ◽  
Single Flow ◽  
And Control ◽  
Muscle Contractile

Muscle contractile activity is associated with an acceleration of glucose transport into muscle. It has been reported that the acceleration of glucose uptake by contractile activity in perfused rat muscles requires the presence of insulin in the perfusate. This claim was investigated using the perfused rat hindlimb preparation in the present study. Rats were made diabetic by injection of 125 mg/kg of streptozotocin and either studied 72 h later or maintained on insulin for 2 wk and then studied 3 days after cessation of insulin therapy. Only rats with plasma insulin levels too low to measure were used. The hindlimbs were washed out with 630 ml of medium over 75 min using a single flow-through washout before muscle stimulation. Despite the absence of insulin in the perfusion medium, stimulation of muscle contraction resulted in large increases in glucose uptake in both the diabetic and control rats. These findings do not support the claim that the stimulatory effect of muscle contraction on glucose uptake by perfused rat muscles requires the presence of insulin.

scholarly journals Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

2020 ◽  
Vol 21 (4) ◽  
pp. 1514 ◽  
Author(s):  
Paul T. Reidy ◽  
Ziad S. Mahmassani ◽  
Alec I. McKenzie ◽  
Jonathan J. Petrocelli ◽  
Scott A. Summers ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Skeletal Muscle Insulin Resistance ◽  
Ceramide Content ◽  
Subcellular Compartmentalization ◽  
Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

AMPKα2 deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle

2011 ◽  
Vol 111 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Marcia J. Abbott ◽  
Lindsey D. Bogachus ◽  
Lorraine P. Turcotte
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Time Dependent ◽  
Substrate Uptake ◽  
Dependent Manner ◽  
Mouse Muscle ◽  
Uptake Rates ◽  
Intracellular Ca

AMP-activated protein kinase (AMPK) is a fuel sensor in skeletal muscle with multiple downstream signaling targets that may be triggered by increases in intracellular Ca2+ concentration ([Ca2+]). The purpose of this study was to determine whether increases in intracellular [Ca2+] induced by caffeine act solely via AMPKα2 and whether AMPKα2 is essential to increase glucose uptake, fatty acid (FA) uptake, and FA oxidation in contracting skeletal muscle. Hindlimbs from wild-type (WT) or AMPKα2 dominant-negative (DN) transgene mice were perfused during rest ( n = 11), treatment with 3 mM caffeine ( n = 10), or muscle contraction ( n = 11). Time-dependent effects on glucose and FA uptake were uncovered throughout the 20-min muscle contraction perfusion period ( P < 0.05). Glucose uptake rates did not increase in DN mice during muscle contraction until the last 5 min of the protocol ( P < 0.05). FA uptake rates were elevated at the onset of muscle contraction and diminished by the end of the protocol in DN mice ( P < 0.05). FA oxidation rates were abolished in the DN mice during muscle contraction ( P < 0.05). The DN transgene had no effect on caffeine-induced FA uptake and oxidation ( P > 0.05). Glucose uptake rates were blunted in caffeine-treated DN mice ( P < 0.05). The DN transgene resulted in a greater use of intramuscular triglycerides as a fuel source during muscle contraction. The DN transgene did not alter caffeine- or contraction-mediated changes in the phosphorylation of Ca2+/calmodulin-dependent protein kinase I or ERK1/2 ( P > 0.05). These data suggest that AMPKα2 is involved in the regulation of substrate uptake in a time-dependent manner in contracting muscle but is not necessary for regulation of FA uptake and oxidation during caffeine treatment.

Glucose uptake by diaphragms from rats subjected to hemorrhagic shock

1964 ◽  
Vol 206 (2) ◽  
pp. 317-320 ◽  
Author(s):  
William R. Drucker ◽  
John C. DeKiewiet
Keyword(s):  
Skeletal Muscle ◽  
Hemorrhagic Shock ◽  
Glucose Uptake ◽  
Anaerobic Metabolism ◽  
Lactate Production ◽  
Bicarbonate Buffer ◽  
Metabolic Alterations ◽  
Shock Models ◽  
The Media ◽  
Intracellular Energy

The marked metabolic alterations that occur in hemorrhagic shock have been ascribed to tissue anoxia occasioned by hypovolemia. Other investigators, utilizing different shock models, have explained the initial metabolic changes as secondary to humoral changes. In skeletal muscle, anoxia is known to cause an increased glucose uptake, whereas epinephrine causes a decreased uptake. The present work was undertaken to explore some alterations in carbohydrate metabolism during hemorrhagic shock in rats, when both tissue anoxia and an altered humoral state are present. Hemidiaphragms from rats subjected to a standardized hemorrhagic shock procedure and from control rats were excised and incubated aerobically in bicarbonate buffer containing glucose. After 1 hr of incubation aliquots of the media were analyzed for glucose and lactate. The results demonstrated a significantly greater glucose uptake and lactate production by the diaphragms from the bled rats. The data suggest that, during hemorrhagic shock in rats, tissue anoxia leads to a predominance of anaerobic metabolism and a severe depletion of intracellular energy, resulting in an increased uptake of glucose in skeletal muscle despite the concomitant altered humoral state which ordinarily would inhibit glucose uptake.

Prolonged suppression of glucose metabolism causes insulin resistance in rat skeletal muscle

1997 ◽  
Vol 272 (2) ◽  
pp. E288-E296 ◽  
Author(s):  
J. K. Kim ◽  
J. H. Youn
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Skeletal Muscles ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Metabolic Fluxes ◽  
Phosphate Inhibition ◽  
Intracellular Glucose

To determine whether an impairment of intracellular glucose metabolism causes insulin resistance, we examined the effects of suppression of glycolysis or glycogen synthesis on whole body and skeletal muscle insulin-stimulated glucose uptake during 450-min hyperinsulinemic euglycemic clamps in conscious rats. After the initial 150 min to attain steady-state insulin action, animals received an additional infusion of saline, Intralipid and heparin (to suppress glycolysis), or amylin (to suppress glycogen synthesis) for up to 300 min. Insulin-stimulated whole body glucose fluxes were constant with saline infusion (n = 7). In contrast, Intralipid infusion (n = 7) suppressed glycolysis by approximately 32%, and amylin infusion (n = 7) suppressed glycogen synthesis by approximately 45% within 30 min after the start of the infusions (P < 0.05). The suppression of metabolic fluxes increased muscle glucose 6-phosphate levels (P < 0.05), but this did not immediately affect insulin-stimulated glucose uptake due to compensatory increases in other metabolic fluxes. Insulin-stimulated whole body glucose uptake started to decrease at approximately 60 min and was significantly decreased by approximately 30% at the end of clamps (P < 0.05). Similar patterns of changes in insulin-stimulated glucose fluxes were observed in individual skeletal muscles. Thus the suppression of intracellular glucose metabolism caused decreases in insulin-stimulated glucose uptake through a cellular adaptive mechanism in response to a prolonged elevation of glucose 6-phosphate rather than the classic mechanism involving glucose 6-phosphate inhibition of hexokinase.

scholarly journals The effects of muscle contraction and insulin on glucose-transporter translocation in rat skeletal muscle

1994 ◽  
Vol 297 (3) ◽  
pp. 539-545 ◽  
Author(s):  
J T Brozinick ◽  
G J Etgen ◽  
B B Yaspelkis ◽  
J L Ivy
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Protein Distribution ◽  
Sprague Dawley ◽  
Glut 4

The effect of electrically induced muscle contraction, insulin (10 m-units/ml) and electrically-induced muscle contraction in the presence of insulin on insulin-regulatable glucose-transporter (GLUT-4) protein distribution was studied in female Sprague-Dawley rats during hindlimb perfusion. Plasma-membrane cytochalasin B binding increased approximately 2-fold, whereas GLUT-4 protein concentration increased approximately 1.5-fold above control with contractions, insulin, or insulin + contraction. Microsomal-membrane cytochalasin B binding and GLUT-4 protein concentration decreased by approx. 30% with insulin or insulin + contraction, but did not significantly decrease with contraction alone. The rate of muscle glucose uptake was assessed by determining the rate of 2-deoxy[3H]glucose accumulation in the soleus, plantaris, and red and white portions of the gastrocnemius. Both contraction and insulin increased glucose uptake significantly and to the same degree in the muscles examined. Insulin + contraction increased glucose uptake above that of insulin or contraction alone, but this effect was only statistically significant in the soleus, plantaris and white gastrocnemius. The combined effects of insulin + contraction of glucose uptake were not fully additive in any of the muscles investigated. These results suggest that (1) insulin and muscle contraction are mobilizing two separate pools of GLUT-4 protein, and (2) the increase in skeletal-muscle glucose uptake due to insulin + contraction is not due to an increase in plasma-membrane GLUT-4 protein concentration above that observed for insulin or contraction alone.

Overexpression or ablation of JNK in skeletal muscle has no effect on glycogen synthase activity

2004 ◽  
Vol 287 (1) ◽  
pp. C200-C208 ◽  
Author(s):  
Nobuharu Fujii ◽  
Marni D. Boppart ◽  
Scott D. Dufresne ◽  
Patricia F. Crowley ◽  
Alison C. Jozsi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Glycogen Synthase ◽  
Contractile Activity ◽  
S6 Kinase ◽  
Jnk Signaling ◽  
Phosphorylation State ◽  
Mouse Skeletal Muscle ◽  
Major Mechanism ◽  
Glycogen Synthase Activity

c-Jun NH2-terminal kinase (JNK) is highly expressed in skeletal muscle and is robustly activated in response to muscle contraction. Little is known about the biological functions of JNK signaling in terminally differentiated muscle cells, although this protein has been proposed to regulate insulin-stimulated glycogen synthase activity in mouse skeletal muscle. To determine whether JNK signaling regulates contraction-stimulated glycogen synthase activation, we applied an electroporation technique to induce JNK overexpression (O/E) in mouse skeletal muscle. Ten days after electroporation, in situ muscle contraction increased JNK activity 2.6-fold in control muscles and 15-fold in the JNK O/E muscles. Despite the enormous activation of JNK activity in JNK O/E muscles, contraction resulted in similar increases in glycogen synthase activity in control and JNK O/E muscles. Consistent with these findings, basal and contraction-induced glycogen synthase activity was normal in muscles of both JNK1- and JNK2-deficient mice. JNK overexpression in muscle resulted in significant alterations in the basal phosphorylation state of several signaling proteins, such as extracellular signal-regulated kinase 1/2, p90 S6 kinase, glycogen synthase kinase 3, protein kinase B/Akt, and p70 S6 kinase, in the absence of changes in the expression of these proteins. These data suggest that JNK signaling regulates the phosphorylation state of several kinases in skeletal muscle. JNK activation is unlikely to be the major mechanism by which contractile activity increases glycogen synthase activity in skeletal muscle.

Invited Review: Intracellular signaling in contracting skeletal muscle

2002 ◽  
Vol 93 (1) ◽  
pp. 369-383 ◽  
Author(s):  
Kei Sakamoto ◽  
Laurie J. Goodyear
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Physical Exercise ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Glycogen Synthase ◽  
Contractile Activity ◽  
Glycogen Synthesis ◽  
Mitogen Activated Protein Kinase ◽  
Molecular Signaling

Physical exercise is a significant stimulus for the regulation of multiple metabolic and transcriptional processes in skeletal muscle. For example, exercise increases skeletal muscle glucose uptake, and, after exercise, there are increases in the rates of both glucose uptake and glycogen synthesis. A single bout of exercise can also induce transient changes in skeletal muscle gene transcription and can alter rates of protein metabolism, both of which may be mechanisms for chronic adaptations to repeated bouts of exercise. A central issue in exercise biology is to elucidate the underlying molecular signaling mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we summarize research from the past several years that has demonstrated that physical exercise can regulate multiple intracellular signaling cascades in skeletal muscle. It is now well established that physical exercise or muscle contractile activity can activate three of the mitogen-activated protein kinase signaling pathways, including the extracellular signal-regulated kinase 1 and 2, the c-Jun NH2-terminal kinase, and the p38. Exercise can also robustly increase activity of the AMP-activated protein kinase, as well as several additional molecules, including glycogen synthase kinase 3, Akt, and the p70 S6 kinase. A fundamental goal of signaling research is to determine the biological consequences of exercise-induced signaling through these molecules, and this review also provides an update of progress in this area.

scholarly journals GLUCOSE METABOLISM OF THE SWIMBLADDER TISSUE OF THE EUROPEAN EEL ANGUILLA ANGUILLA

1993 ◽  
Vol 185 (1) ◽  
pp. 169-178 ◽  
Author(s):  
B. Pelster ◽  
P. Scheid
Keyword(s):  
Glucose Uptake ◽  
Venous Blood ◽  
Lactate Concentration ◽  
Lactate Production ◽  
Anguilla Anguilla ◽  
Pentose Phosphate ◽  
Co2 Production ◽  
European Eel ◽  
O2 Uptake ◽  
Lactate Release

Glucose uptake from, and lactate release into, the blood have been analysed in the active gas- depositing swimbladder of the immobilized European eel Anguilla anguilla. Under normoxic conditions, 0.72 micromole min-1 glucose was removed from the blood supply, while lactate was released into it at a rate of 1.16 micromole min-1. The rate of gas deposition into the swimbladder was significantly correlated with the rate of lactate production. Under hypoxic conditions, glucose consumption by, and lactate production of, the swimbladder tissue were reduced, as was the rate of gas deposition. Compared with normoxic conditions, lactate concentration in the swimbladder tissue was elevated after 1 h of hypoxia, indicating a decrease in lactate release. No difference in the osmolality of arterial and venous blood could be detected in these experiments. Combining the data for glucose uptake and lactate release measured under normoxic conditions with the values for O2 uptake and CO2 production of the swimbladder tissue measured under similar conditions in a previous study, a quantitative evaluation of glucose catabolism was performed. According to the O2 uptake of the tissue, only about 1 % of the glucose was oxidized, while about 80 % was fermented to lactic acid. The remaining 0.14 micromole min-1 glucose was presumably catabolized through the pentose phosphate shunt, as indicated by the CO2 production of 0.16 micromole min-1 that cannot be explained by aerobic metabolism.

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