scholarly journals Effects of epinephrine on glucose metabolism in contracting rat skeletal muscles

1998 ◽  
Vol 275 (3) ◽  
pp. E448-E456 ◽  
Author(s):  
Rune Aslesen ◽  
Jørgen Jensen

The effects of epinephrine on glucose metabolism during contractile activity and insulin stimulation were investigated in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles from Wistar rats. All muscles were mounted on contraction apparatuses, and some muscles were stimulated electrically for 30 min in vitro. Glucose uptake and glucose phosphorylation were measured with 2-[1,2-3H(N)]deoxy-d-glucose and glucose transport with 3- O-[ methyl-3H]methyl-d-glucose.d-[1-14C]mannitol was used to correct for extracellular space. In epitrochlearis, both contraction and insulin increased glucose transport by threefold, and combined they showed an additive effect. Epinephrine (10−6 M) did not influence glucose transport across the membrane during contractile activity or insulin stimulation. In the absence of epinephrine, similar glucose phosphorylation was obtained during contraction and during insulin stimulation in epitrochlearis (∼12 mmol ⋅ kg dry wt−1 ⋅ 30 min−1). In the presence of epinephrine, 9.5 ± 0.6 mmol ⋅ kg dry wt−1 ⋅ 30 min−1 glucose was phosphorylated during contraction, whereas only 2.0 ± 0.3 mmol ⋅ kg dry wt−1 ⋅ 30 min−1 was phosphorylated during insulin stimulation ( P < 0.01), despite a similar glucose 6-phosphate concentration. Comparable results were obtained in soleus. In conclusion, our data suggest that epinephrine inhibits glucose phosphorylation much less during contraction than during insulin stimulation.

1995 ◽  
Vol 268 (1) ◽  
pp. C30-C35 ◽  
Author(s):  
P. Hansen ◽  
E. Gulve ◽  
J. Gao ◽  
J. Schluter ◽  
M. Mueckler ◽  
...  

There is some controversy regarding whether insulin or contractile activity alters the affinity of skeletal muscle glucose transporters for glucose and its analogues. The effects of insulin and contractions on the kinetics of glucose transport were therefore reexamined in isolated rat skeletal muscles. Concentration-dependent rates of 2-deoxyglucose (2-DG) transport were measured in the absence or presence of insulin (2 mU/ml) in the epitrochlearis and split soleus muscles. The apparent half-maximal saturating substrate concentration (Km) for basal 2-DG transport (approximately 12 mM) was similar for the split soleus and epitrochlearis, and the apparent Km was not changed by insulin in either muscle type. The presence of 2 mU/ml insulin increased the maximal transport velocity (Vmax) approximately fourfold in the epitrochlearis and approximately eightfold in the split soleus. In the epitrochlearis, in vitro muscle contractions also resulted in an approximately fourfold increases in Vmax with no change in apparent Km. The combined effects of insulin and contractions on Vmax were completely additive, but the apparent Km was not different from insulin alone. The apparent Km values for basal and insulin-stimulated glucose transport were further characterized in the epitrochlearis isolated from transgenic mice overexpressing the GLUT-1 isoform in the sarcolemma and their nontransgenic littermates. The apparent Km for basal 2-DG transport in the transgenic muscle (9 mM) was not significantly different from the apparent Km for insulin-stimulated transport in the control muscle (10 mM). The present study provides evidence that insulin and contractions, either alone or in combination, increase glucose transport activity in skeletal muscle by increasing Vmax, with no significant change in Km. Our results also suggest that, in intact skeletal muscle, the Km for basal glucose transport (a process mediated primarily by GLUT-1) is similar to the Km values for stimulated transport, mediated predominantly by GLUT-4.


2004 ◽  
Vol 287 (2) ◽  
pp. E305-E309 ◽  
Author(s):  
David C. Wright ◽  
Paige C. Geiger ◽  
Mark J. Rheinheimer ◽  
Dong Ho Han ◽  
John O. Holloszy

Recent evidence has shown that activation of lipid-sensitive protein kinase C (PKC) isoforms leads to skeletal muscle insulin resistance. However, earlier studies demonstrated that phorbol esters increase glucose transport in skeletal muscle. The purpose of the present study was to try to resolve this discrepancy. Treatment with the phorbol ester 12-deoxyphorbol-13-phenylacetate 20-acetate (dPPA) led to an ∼3.5-fold increase in glucose transport in isolated fast-twitch epitrochlearis and flexor digitorum brevis muscles. Phorbol ester treatment was additive to a maximally effective concentration of insulin in fast-twitch skeletal muscles. Treatment with dPPA did not affect insulin signaling in the epitrochlearis. In contrast, phorbol esters had no effect on basal glucose transport and inhibited maximally insulin-stimulated glucose transport ∼50% in isolated slow-twitch soleus muscle. Furthermore, dPPA treatment inhibited the insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the threonine and serine phosphorylation of PKB by ∼50% in the soleus. dPPA treatment also caused serine phosphorylation of IRS-1 in the slow-twitch soleus muscle. In conclusion, our results show that phorbol esters stimulate glucose transport in fast-twitch skeletal muscles and inhibit insulin signaling in slow-twitch soleus muscle of rats. These findings suggest that mechanisms other than PKC activation mediate lipotoxicity-induced whole body insulin resistance.


1994 ◽  
Vol 19 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Arend Bonen ◽  
Karl J. A. McCullagh

Skeletal muscle lactate transport was investigated in vitro in isolated fast-twitch (EDL) and slow-twitch soleus (Sol) skeletal muscles from control and exercised mice. Exercise (23 m/min, 8% grade) reduced muscle glycogen by 37% in EDL (p < 0.05) and by 35% in Sol muscles (p < 0.05). Lactate transport measurements (45 sec) were performed after 60 min of exercise in intact EDL and Sol muscles in vitro, at differing pH (6.5 and 7.4) and differing lactate concentrations (4 and 30 mM). Lactate transport was observed to be greater in Sol than in EDL (p < 0.05). In the exercised muscles there was a small but significant increase in lactate transport (p < 0.05). Lactate transport was greater when exogenous lactate concentrations were greater (p < 0.05) and more rapid at the lower pH (p < 0.05). These studies demonstrated that lactate transport was increased with exercise. Key words: soleus, EDL, treadmill exercise


1987 ◽  
Vol 65 (4) ◽  
pp. 697-703 ◽  
Author(s):  
Roberto T. Sudo ◽  
Gisele Zapata ◽  
Guilherme Suarez-Kurtz

The characteristics of transient contractures elicited by rapid cooling of frog or mouse muscles perfused in vitro with solutions equilibrated with 0.5–2.0% halothane are reviewed. The data indicate that these halothane-cooling contractures are dose dependent and reproducible, and their amplitude is larger in muscles containing predominantly slow-twitch type fibers, such as the mouse soleus, than in muscles in which fast-twitch fibers predominate, such as the mouse extensor digitorum longus. The halothane-cooling contractures are potentiated in muscles exposed to succinylcholine. The effects of Ca2+-free solutions, of the local anesthetics procaine, procainamide, and lidocaine, and of the muscle relaxant dantrolene on the halothane-cooling contractures are consistent with the proposal that the halothane-cooling contractures result from synergistic effects of halothane and low temperature on Ca sequestration by the sarcoplasmic reticulum. Preliminary results from skinned rabbit muscle fibers support this proposal. The halothane concentrations required for the halothane-cooling contractures of isolated frog or mouse muscles are comparable with those observed in serum of patients during general anesthesia. Accordingly, fascicles dissected from muscle biopsies of patients under halothane anesthesia for programmed surgery develop large contractures when rapidly cooled. The amplitude of these halothane-cooling contractures declined with the time of perfusion of the muscle fascicles in vitro with halothane-free physiological solutions. It is suggested that the halothane-cooling contractures could be used as a simple experimental model for the investigation of the effects of halothane on Ca homeostasis and contractility in skeletal muscle and for study of drugs of potential use in the management of the contractures associated with the halothane-induced malignant hyperthermia syndrome. It is shown that salicylates, but not indomethacin or mefenamic acid, inhibit the halothane-cooling contractures.


1993 ◽  
Vol 264 (3) ◽  
pp. E319-E327 ◽  
Author(s):  
E. A. Gulve ◽  
E. J. Henriksen ◽  
K. J. Rodnick ◽  
J. H. Youn ◽  
J. O. Holloszy

It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT-4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS)


1996 ◽  
Vol 271 (6) ◽  
pp. E1061-E1066 ◽  
Author(s):  
D. Meynial-Denis ◽  
M. Mignon ◽  
A. Miri ◽  
J. Imbert ◽  
E. Aurousseau ◽  
...  

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.


1983 ◽  
Vol 245 (1) ◽  
pp. R25-R31 ◽  
Author(s):  
G. Sjogaard

Sodium, potassium, and magnesium were analyzed in human slow-twitch (ST) and fast-twitch (FT) skeletal muscles. In contrast to other species, no relation was found between fiber composition and electrolyte distribution. In soleus (S), vastus lateralis (VL), and triceps brachii (TB) the overall mean values for 6 men and 6 women were 44 mmol K/100 g dry wt and 11 mmol Na/100 g dry wt; the intracellular concentrations were 161 mmol K/l and 26 mmol Na/l with no differences between the muscles. Analysis of fragments of single ST and FT fibers from each of the muscles also showed no difference between the fiber types in Na and K content. Small differences were seen between the muscles with regard to Mg, but these were not related to fiber composition compared with other species. During exercise to exhaustion (3 bouts of bicycling for 3 min at 325-395 W, 6 men) the extracellular electrolyte concentrations for Na, K, and Mg increased from 134 to 140, 4.5 to 5.8, and 0.75 to 0.87 mmol/l, respectively (P less than 0.05). In VL Na content increased from 9.8 to 16.5 mmol/100 g dry wt, while intracellular [Na] remained constant. In contrast, intracellular [K] decreased from 161 to 141 mmol/l (P less than 0.05). No such changes occurred in TB. In concert with other studies the present changes in electrolytes in the working muscles indicate that muscle fatigue may be related to changes at the muscle fiber membrane.


1984 ◽  
Vol 57 (1) ◽  
pp. 246-253 ◽  
Author(s):  
S. M. Sullivan ◽  
R. N. Pittman

In vitro oxygen consumption (VO2), histochemical fiber type, capillary arrangement, and muscle fiber geometry were measured in three hamster striated muscles. These muscles varied markedly in their histochemical fiber type composition (% by number): retractor (70% FG, fast-twitch, glycolytic; 16% FOG, fast-twitch, oxidative-glycolytic; 14% SO, slow-twitch, oxidative); soleus (57% FOG, 43% SO), and sartorius (98% FG, 2% FOG). Sartorius VO2 [0.80 +/- 0.034 (SE) ml O2 X min-1 X 100 g-1] was significantly different (P less than 0.01) from VO2 of retractor (0.89 +/- 0.038) and soleus (1.00 +/- 0.048).The number of capillaries around a fiber and the surface area/volume were greater for FOG and SO fibers than for FG fibers. Fibers of all types appeared to be roughly elliptical in shape. Capillaries were uniformly distributed around fibers in the soleus, but they were located more toward the ends of the major diameter in the retractor and sartorius. The results suggest a relationship among a fiber's oxidative capacity (based on its histochemical staining pattern), number of surrounding capillaries and surface area/volume. Furthermore, results suggest that VO2 and capillary spacing around a fiber may depend on fiber type.


1980 ◽  
Vol 239 (6) ◽  
pp. E454-E460 ◽  
Author(s):  
R. Nesher ◽  
I. E. Karl ◽  
K. E. Kaiser ◽  
D. M. Kipnis

An in vitro rat muscle preparation is described that can contract at rates of 12–240 twitches/min. Maximum dF/dt paralleled maximum twitch tension, their ratio being constant at approximately 8 ms for contraction rates of 12-120 twitches/min. Time to peak tension was 8–13 ms, time to peak dF/dt 5–8 ms, and half-relaxation time 4 ms. These parameters were unaffected by rate of contraction or duration of isometric work. Differential ATPase staining demonstrated that 60–65% of the fibers were fast-twitch white, 20% fast-twitch red, and 15% slow-twitch red. The preponderance of fast-twitch fibers correlated with the observed mechanical performance of the muscle. Muscles contracting for 60 min at rates up to 48 twitches/min maintained total adenine nucleotide content (ATP, ADP, AMP) at near resting levels. At higher twitch rates (72–240 twitches/min), total adenine nucleotide content decreased 40%, reflecting exclusively a fall in ATP in the presence of adequate phosphocreatine stores. Adequate oxygenation was reflected by lactate-to-pyruvate ratios in the range of 11–15 at all rates of contraction.


1985 ◽  
Vol 59 (3) ◽  
pp. 916-923 ◽  
Author(s):  
R. H. Fitts ◽  
C. J. Brimmer

Contractile properties of slow-twitch soleus (SOL), fast-twitch extensor digitorum longus (EDL), and fast-twitch superficial region of the vastus lateralis were determined in vitro (22 degrees C) in rats remobilized after prolonged (3 mo) hindlimb immobilization (IM). For all muscles the muscle-to-body weight ratio was significantly depressed by IM, and the ratios failed to completely recover even after 90 days. The contractile properties of the fast-twitch muscles were less affected by IM than the slow-twitch SOL. The IM shortened the SOL isometric twitch duration due to a reduced contraction and half-relaxation time. These parameters returned to control levels by the 14th day of recovery. Peak tetanic tension (Po, g/cm2) declined with IM by 46% in the SOL but showed no significant change in the fast-twitch muscles. After IM the SOL Po (g/cm2) recovered to control values by 28 days. The recovery of Po in absolute units (g) was considerably slower and did not return to control levels until 60 (SOL) to 90 (EDL) days. The maximum shortening velocity was not altered by IM in any of the muscles studied. These results demonstrate that both fast- and slow-twitch skeletal muscles possess the ability to completely recover normal contractile function following prolonged periods of hindlimb IM.


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