Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle

2002 ◽  
Vol 282 (6) ◽  
pp. E1291-E1300 ◽  
Author(s):  
Hua Ai ◽  
Jacob Ihlemann ◽  
Ylva Hellsten ◽  
Hans P. M. M. Lauritzen ◽  
D. Grahame Hardie ◽  
...  

AMP-activated protein kinase (AMPK) may mediate the stimulatory effect of contraction and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on glucose transport in skeletal muscle. In muscles with different fiber type composition from fasted rats, AICAR increased 2-deoxyglucose transport and total AMPK activity approximately twofold in epitrochlearis (EPI), less in flexor digitorum brevis, and not at all in soleus muscles. Contraction increased both transport and AMPK activity more than AICAR did. In EPI muscles, the effects of AICAR and contractions on glucose transport were partially additive despite a lower AMPK activity with AICAR compared with contraction alone. In EPI from fed rats, glucose transport responses were smaller than what was seen in fasted rats, and AICAR did not increase transport despite an increase in AMPK activity. AICAR and contraction activated both α1- and α2-isoforms of AMPK. Expression of both isoforms varied with fiber types, and α2 was highly expressed in nuclei. In conclusion, AICAR-stimulated glucose transport varies with muscle fiber type and nutritional state. AMPK is unlikely to be the sole mediator of contraction-stimulated glucose transport.

2003 ◽  
Vol 285 (4) ◽  
pp. E836-E844 ◽  
Author(s):  
Hua Ai ◽  
Evelyn Ralston ◽  
Hans P. M. M. Lauritzen ◽  
Henrik Galbo ◽  
Thorkil Ploug

Insulin and muscle contractions stimulate glucose transport in skeletal muscle through a translocation of intracellular GLUT4 glucose transporters to the cell surface. Judged by immunofluorescence microscopy, part of the GLUT4 storage sites is associated with the extensive microtubule cytoskeleton found in all muscle fibers. Here, we test whether microtubules are required mediators of the effect of insulin and contractions. In three different incubated rat muscles with distinct fiber type composition, depolymerization of microtubules with colchicine for ≤8 h did not inhibit insulin- or contraction-stimulated 2-deoxyglucose transport or force production. On the contrary, colchicine at least partially prevented the ∼30% decrease in insulin-stimulated transport that specifically developed during 8 h of incubation in soleus muscle but not in flexor digitorum brevis or epitrochlearis muscles. In contrast, nocodazole, another microtubule-disrupting drug, rapidly and dose dependently blocked insulin- and contraction-stimulated glucose transport. A similar discrepancy between colchicine and nocodazole was also found in their ability to block glucose transport in muscle giant “ghost” vesicles. This suggests that the ability of insulin and contractions to stimulate glucose transport in muscle does not require an intact microtubule network and that nocodazole inhibits glucose transport independently of its microtubule-disrupting effect.


2000 ◽  
Vol 279 (4) ◽  
pp. E862-E867 ◽  
Author(s):  
Jacob Ihlemann ◽  
Thorkil Ploug ◽  
Ylva Hellsten ◽  
Henrik Galbo

Previous studies have indicated that frequency of stimulation is a major determinant of glucose transport in contracting muscle. We have now studied whether this is so also when total force development or metabolic rate is kept constant. Incubated soleus muscles were electrically stimulated to perform repeated tetanic contractions at four different frequencies (0.25, 0.5, 1, and 2 Hz) for 10 min. Resting length was adjusted to achieve identical total force development or metabolic rate (glycogen depletion and lactate accumulation). Overall, at constant total force development, glucose transport (2-deoxyglucose uptake) increased with stimulation frequency ( P < 0.05; basal: 25 ± 2, 0.25 Hz: 50 ± 4, 0.5 Hz: 50 ± 3, 1 Hz: 81 ± 5, 2 Hz: 79 ± 3 nmol · g−1 · 5 min−1). However, glucose transport was identical ( P > 0.05) at the two lower (0.25 and 0.5 Hz) as well as at the two higher (1 and 2 Hz) frequencies. Glycogen decreased ( P < 0.05; basal: 19 ± 1, 0.25 Hz: 13 ± 1, 0.5 Hz: 12 ± 2, 1 Hz: 7 ± 1, 2 Hz: 7 ± 1 mmol/kg) and 5′-AMP-activated protein kinase (AMPK) activity increased ( P < 0.05; basal: 1.7 ± 0.4, 0.25 Hz: 32.4 ± 7.0, 0.5 Hz: 36.5 ± 2.1, 1 Hz: 63.4 ± 8.0, 2 Hz: 67.0 ± 13.4 pmol · mg−1 · min−1) when glucose transport increased. Experiments with constant metabolic rate were carried out in soleus, flexor digitorum brevis, and epitrochlearis muscles. In all muscles, glucose transport was identical at 0.5 and 2 Hz ( P > 0.05); also, AMPK activity did not increase with stimulation frequency. In conclusion, muscle glucose transport increases with stimulation frequency but only in the face of energy depletion and increase in AMPK activity. This indicates that contraction-induced glucose transport is elicited by metabolic demands rather than by events occurring early during the excitation-contraction coupling.


2015 ◽  
Vol 308 (6) ◽  
pp. R467-R479 ◽  
Author(s):  
David Selvin ◽  
Erik Hesse ◽  
Jean-Marc Renaud

The objective of this study was to optimize the approach to obtain viable single flexor digitorum brevis (FDB) fibers following a collagenase digestion. A first aim was to determine the culture medium conditions for the collagenase digestion. The MEM yielded better fibers in terms of morphology and contractility than the DMEM. The addition of FBS to culture media was crucial to prevent fiber supercontraction. The addition of FBS to the physiological solution used during an experiment was also beneficial, especially during fatigue. Optimum FBS concentration in MEM was 10% (vol/vol), and for the physiological solution, it ranged between 0.2 and 1.0%. A second aim was to document the stability of single FDB fibers. If tested the day of the preparation, most fibers (∼80%) had stable contractions for up to 3 h, normal stimulus duration strength to elicit contractions, and normal and stable resting membrane potential during prolonged microelectrode penetration. A third aim was to document their fatigue kinetics. Major differences in fatigue resistance were observed between fibers as expected from the FDB fiber-type composition. All sarcoplasmic [Ca2+] and sarcomere length parameters returned to their prefatigue levels after a short recovery. The pCa-sarcomere shortening relationship of unfatigued fibers is very similar to the pCa-force curve reported in other studies. The pCa-sarcomere shortening from fatigue data is complicated by large decreases in sarcomere length between contractions. It is concluded that isolation of single fibers by a collagenase digestion is a viable preparation to study contractility and fatigue kinetics.


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)


1990 ◽  
Vol 259 (4) ◽  
pp. E593-E598 ◽  
Author(s):  
E. J. Henriksen ◽  
R. E. Bourey ◽  
K. J. Rodnick ◽  
L. Koranyi ◽  
M. A. Permutt ◽  
...  

The relationships among fiber type, glucose transporter (GLUT-4) protein content, and glucose transport activity stimulated maximally with insulin and/or contractile activity were studied by use of the rat epitrochlearis (15% type I-20% type II2a-65% type IIb), soleus (84-16-0%), extensor digitorum longus (EDL, 3-57-40%), and flexor digitorum brevis (FDB, 7-92-1%) muscles. Insulin-stimulated 2-deoxy-D-glucose (2-DG) uptake was greatest in the soleus, followed (in order) by the FDB, EDL, and epitrochlearis. On the other hand, contractile activity induced the greatest increase in 2-DG uptake in the FDB, followed by the EDL, soleus, and epitrochlearis. The effects of insulin and contractile activity on 2-DG uptake were additive in all the muscle preparations, with the relative rates being FDB greater than soleus greater than EDL greater than epitrochlearis. Quantitation of the GLUT-4 protein content with the antiserum R820 showed the following pattern: FDB greater than soleus greater than EDL greater than epitrochlearis. Linear regression analysis showed that whereas a relatively low and nonsignificant correlation existed between GLUT-4 protein content and 2-DG uptake stimulated by insulin alone, significant correlations existed between GLUT-4 protein content and 2-DG uptake stimulated either by contractions alone (r = 0.950) or by insulin and contractions in combination (r = 0.992). These results suggest that the differences in maximally stimulated glucose transport activity among the three fiber types may be related to differences in their content of GLUT-4 protein.


2012 ◽  
Vol 22 (4) ◽  
pp. 292-303 ◽  
Author(s):  
Ildus I. Ahmetov ◽  
Olga L. Vinogradova ◽  
Alun G. Williams

The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5–90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40–50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin–NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.


1996 ◽  
Vol 81 (1) ◽  
pp. 152-155 ◽  
Author(s):  
Y. Ohira ◽  
W. Yasui ◽  
F. Kariya ◽  
T. Tanaka ◽  
I. Kitajima ◽  
...  

Effects of 14 days of spaceflight on beta-adrenoceptor (beta-AR), mitochondrial enzyme activities, and fiber type composition were studied in plantaris muscles of male adult Sprague-Dawley rats. The beta-AR was analyzed in cross sections by quantitative autoradiography. The maximum binding capacity (Bmax) of beta-AR was significantly lowered (approximately 29%) after flight, but the recovery was not completed within 9 days in 1-G environment. Because the dissociation constant remained unchanged, it is suggested that the changes in the Bmax were caused by the alteration of receptor number. The activities of succinate dehydrogenase (SDH) measured in whole homogenates were subnormal (approximately -24%) in muscles sampled approximately 5 h after flight but they were normalized during 9 days of recovery. The percent composition of fiber types and beta-hydroxyacyl CoA dehydrogenase (HAD) activity did not change significantly due to spaceflight. It is suggested that the spaceflight-induced decrease of the Bmax of beta-AR in plantaris was accompanied by a lowered activity of a mitochondrial inner-membrane enzyme SDH but not a matrix enzyme HAD.


1994 ◽  
Vol 266 (6) ◽  
pp. E946-E952 ◽  
Author(s):  
G. D. Cartee ◽  
D. J. Dean

The time course (1, 5, or 20 days) for the effect of dietary restriction (DR; approximately 25% reduction below ad libitum intake) on epitrochlearis and flexor digitorum brevis (FDB) muscle glucose transport activity was studied in female Fischer 344 rats (8 mo old). Epitrochlearis glucose transport activity with 100 microU/ml insulin was increased by 38% after 5 days of DR (P < 0.05) despite no change in glucose transport activity with 0 or 20,000 microU/ml insulin. The increase with 100 microU/ml insulin was not further enhanced by 20 days of DR. DR did not result in a significant increase in the glucose transport activity of the FDB with 0, 100, or 20,000 microU/ml insulin. Abdominal fat content was significantly (P < 0.01) reduced below ad libitum levels only after 20 days of DR. These results demonstrate that DR-induced improvement in epitrochlearis glucose transport activity with a physiological insulin concentration can occur very rapidly, preceding detectable changes in basal or maximal insulin-stimulated glucose transport activity or abdominal fat pad mass, and the enhancement of insulin action does not occur simultaneously in all muscles.


1998 ◽  
Vol 275 (3) ◽  
pp. E487-E494 ◽  
Author(s):  
Anne Raben ◽  
Elsebeth Mygind ◽  
Arne Astrup

Muscle fiber morphology and activities of four key enzymes, as well as energy metabolism, were determined in nine normal-weight postobese women and nine matched control subjects. No differences in fiber type composition, but a smaller mean fiber area and area of fiber types I and IIb, were found in postobese compared with control subjects ( P < 0.05). The activities of β-hydroxyacyl-CoA dehydrogenase (HADH) and citrate synthase (CS) were 20% lower in postobese than in control subjects ( P < 0.05). However, the activities of lactate dehydrogenase and lipoprotein lipase were not significantly different between postobese and control subjects. Basal metabolic rate and respiratory exchange ratio were also similar, but maximal oxygen uptake (V˙o 2 max) tended to be lower in postobese than in control subjects ( P = 0.06). When adjustments were made for differences inV˙o 2 max, HADH and CS were not different between postobese and control subjects. In conclusion, these data suggest that smaller fiber areas and lower enzyme activities, i.e., markers of aerobic capacity of skeletal muscle, but not fiber composition, may be factors predisposing to obesity.


2017 ◽  
Vol 123 (1) ◽  
pp. 249-259 ◽  
Author(s):  
Luz M. Acevedo ◽  
Ana I. Raya ◽  
Rafael Ríos ◽  
Escolástico Aguilera-Tejero ◽  
José-Luis L. Rivero

A clear picture of skeletal muscle adaptations to obesity and related comorbidities remains elusive. This study describes fiber-type characteristics (size, proportions, and oxidative enzyme activity) in two typical hindlimb muscles with opposite structure and function in an animal model of genetic obesity. Lesser fiber diameter, fiber-type composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of muscle fiber types were assessed in slow (soleus)- and fast (tibialis cranialis)-twitch muscles of obese Zucker rats and compared with age (16 wk)- and sex (females)-matched lean Zucker rats ( n = 16/group). Muscle mass and lesser fiber diameter were lower in both muscle types of obese compared with lean animals even though body weights were increased in the obese cohort. A faster fiber-type phenotype also occurred in slow- and fast-twitch muscles of obese rats compared with lean rats. These adaptations were accompanied by a significant increment in histochemical succinic dehydrogenase activity of slow-twitch fibers in the soleus muscle and fast-twitch fiber types in the tibialis cranialis muscle. Obesity significantly increased plasma levels of proinflammatory cytokines but did not significantly affect protein levels of peroxisome proliferator-activated receptors PPARγ or PGC1α in either muscle. These data demonstrate that, in female Zucker rats, obesity induces a reduction of muscle mass in which skeletal muscles show a diminished fiber size and a faster and more oxidative phenotype. It was noteworthy that this discrepancy in muscle's contractile and metabolic features was of comparable nature and extent in muscles with different fiber-type composition and antagonist functions. NEW & NOTEWORTHY This study demonstrates a discrepancy between morphological (reduced muscle mass), contractile (shift toward a faster phenotype), and metabolic (increased mitochondrial oxidative enzyme activity) characteristics in skeletal muscles of female Zucker fatty rats. It is noteworthy that this inconsistency was comparable (in nature and extent) in muscles with different structure and function.


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