scholarly journals Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat

1977 ◽  
Vol 162 (3) ◽  
pp. 557-568 ◽  
Author(s):  
E Z Maizels ◽  
N B Ruderman ◽  
M N Goodman ◽  
D Lau

1. The effect of acetoacetate on glucose metabolism was compared in the soleus, a slow-twitch red muscle, and the extensor digitorum longus, a muscle composed of 50% fast-twitch red and 50% white fibres. 2. When incubated for 2h in a medium containing 5 mM-glucose and 0.1 unit of insulin/ml, rates of glucose uptake, lactate release and glucose oxidation in the soleus were 19.6, 18.6 and 1.47 micronmol/h per g respectively. Acetoacetate (1.7 mM) diminished all three rates by 25-50%; however, it increased glucose conversion into glycogen. In addition, it caused increases in tissue glucose, glucose 6-phosphate and fructose 6-phosphate, suggesting inhibition of phosphofructokinase. The concentrations of citrate, an inhibitor of phosphofructokinase, and of malate were also increased. 3. Rates of glucose uptake and lactate release in the extensor digitorum longus were 50-80% of those in the soleus. Acetoacetate caused moderate increases in tissue glucose 6-phosphate and possibly citrate, but it did not decrease glucose uptake or lactate release. 4. The rate of glycolysis in the soleus was approximately five times that previously observed in the perfused rat hindquarter, a muscle preparation in which acetoacetate inhibits glucose oxidation, but does not alter glucose uptake or glycolysis. A similar rate of glycolysis was observed when the soleus was incubated with a glucose-free medium. Under these conditions, tissue malate and the lactate/pyruvate ratio in the medium were decreased, and acetoacetate did not decrease lactate release or increase tissue citrate or glucose 6-phosphate. An intermediate rate of glycolysis, which was not decreased by acetoacetate, was observed when the soleus was incubated with glucose, but not insulin. 5. The data suggest that acetoacetate glucose inhibits uptake and glycolysis in red muscle under conditions that resemble mild to moderate exercise. They also suggest that the accumulation of citrate in these circumstances is linked to the rate of glycolysis, possibly through the generation of cytosolic NADH and malate formation.

1996 ◽  
Vol 270 (6) ◽  
pp. R1355-R1360
Author(s):  
E. Johannsson ◽  
O. Waerhaug ◽  
A. Bonen

We determined whether the twitch-velocity phenotype or the metabolic phenotype of a muscle influences the content of GLUT-4 and GLUT-1 proteins. The soleus (Sol) and extensor digitorum longus (EDL) muscles were cross-reinnervated (X-Sol, X-EDL). After 3 mo the X-EDL had become enriched in slow-twitch oxidative (SO) fibers (70.5% SO) compared with its control (3.8% SO), whereas the X-Sol became enriched in fast-twitch oxidative-glycolytic (FOG) fibers (78.6% FOG) compared with its control (10% FOG). Thus the twitch phenotype of X-Sol shifted to fast-twitch muscle, whereas X-EDL shifted to a slow-twitch muscle. In the X-EDL, the oxidative nature of the X-EDL was increased to 97% oxidative fibers compared with 43% oxidative fibers in the normal EDL. In the Sol the oxidative nature of the X-Sol was retained at 100%. GLUT-4 content was increased 1.6-fold in the X-EDL (P < 0.05) but was not changed in the X-Sol (P > 0.05). GLUT-1 content was increased fourfold in X-EDL but was not altered in the X-Sol. We conclude that GLUT-4 and GLUT-1 content in muscle is related to the oxidative phenotype of the muscle rather than the twitch-velocity phenotype.


1982 ◽  
Vol 30 (12) ◽  
pp. 1275-1288 ◽  
Author(s):  
D A Riley ◽  
S Ellis ◽  
J Bain

Carbonic anhydrase (CA) activities were studied in soluble extracts and cryostat sections of skeletal muscles from prepubertal and postpubertal rats. Acetazolamide inhibition was utilized to distinguish between activities of the acetazolamide-sensitive (CA I and II) and acetazolamide-resistant (CA III) forms of the enzyme. The inhibition studies indicated that fast-twitch oxidative-glycolytic muscle fibers contained both the sensitive and resistant forms of CA. Acetazolamide-sensitive activity was localized within muscle fibers, axons, myelin, and capillaries. Axoplasmic staining was restricted to subpopulations of myelinated axons in both the dorsal and ventral roots. Soleus muscles exhibited significantly greater activity of CA III than extensor digitorum longus muscles at all ages examined. CA III was richest in slow-twitch oxidative and intrafusal fibers. During puberty, soleus muscle fibers matured and converted from fast-twitch oxidative-glycolytic to slow-twitch oxidative fibers. There was a shift from the sensitive to the resistant form of CA; CA III activity increased about sevenfold. This activity peaked earlier in the muscles of female rats than male rats. These results demonstrated a complex distribution of CA isozymes in the neuromuscular system and pointed out that isozyme content depends on both the type of muscle and the age and sex of the animal.


1984 ◽  
Vol 62 (12) ◽  
pp. 1500-1504 ◽  
Author(s):  
A. Bonen ◽  
M. H. Tan ◽  
W. M. Watson-Wright

To elucidate the mechanism of enhanced insulin sensitivity by muscle after exercise, we studied insulin binding, 2-deoxy-D-[1-14C]glucose (2-DOG) uptake and [5-3H]glucose utilization in glycolysis and glycogenesis in soleus and extensor digitorum longus (EDL) muscles of mice after 60 min of treadmill exercise. In the soleus, glycogenesis was increased after exercise (P < 0.05) and remained sensitive to the action of insulin. Postexercise insulin-stimulated glycolysis was also increased in the soleus (P < 0.05). In the EDL, glycogenesis was increased after exercise (P < 0.05). However, this was already maximal in the absence of insulin and was not further stimulated by insulin (0.1–4 nM). The disposal of glucose occurred primarily via the glycolytic pathway (>60%) in the soleus and EDL at rest and after exercise. The uptake of 2-DOG uptake was not altered in the soleus after exercise (4 h incubation at 18 °C). However, with 1-h incubations at 37 °C, a marked increase in 2-DOG uptake after exercise was observed in the soleus (P < 0.05) in the absence (0 nM) and presence of insulin (0.2–4 nM) (P < 0.05). A similar postexercise increase in 2-DOG uptake occurred in EDL. Despite the marked increase in glucose uptake and metabolism, no changes in insulin binding were apparent in either EDL or soleus at 37 °C or 18 °C. This study shows that the postexercise increase of glucose disposal does not appear to be directly attributable to increments in insulin binding to slow-twitch and fast-twitch muscles. Also, after exercise the increments in glucose metabolism differ markedly in the two types of muscle.


1990 ◽  
Vol 258 (4) ◽  
pp. E693-E700 ◽  
Author(s):  
A. Bonen ◽  
J. C. McDermott ◽  
M. H. Tan

We examined the effects of selected hormones and pH on the rates of glyconeogenesis (L-[U-14C]-lactate----glycogen) and glycogenesis (D-[U-14C]glucose----glycogen) in mouse fast-twitch (FT) and slow-twitch muscles incubated in vitro (37 degrees C). Glyconeogenesis and glycogenesis increased linearly with increasing concentrations of lactate (5-20 mM) and glucose (2.5-10 mM), respectively, in both muscles. Glyconeogenesis was approximately three- to fourfold greater in the extensor digitorum longus (EDL) than in the soleus, whereas basal glycogenesis was twofold greater in the soleus muscle than in the EDL. Lactate accounted for up to 5% of the glycogen formed in the soleus and up to 32% in the EDL relative to the rates of glycogenesis (i.e., 5 mM glucose + 10 nM insulin) in each muscle. Corticosterone (10(-12)-10(-6) M) failed to alter glyconeogenesis, whereas this hormone reduced glycogenesis. Insulin (10 nM) markedly stimulated glycogenesis but failed to stimulate glyconeogenesis. The rates of both glycogenesis and glyconeogenesis were pH sensitive, with optimal rates at pH 6.5-7.0 in both muscles. Glyconeogenesis increased by 49% in the soleus and by 39% EDL at pH 6.5 compared with pH 7.4. Glycogenesis increased in the soleus (SOL) and EDL in the absence (SOL: +22%; EDL: +52%) and presence of insulin (SOL: +22%; EDL: +51%) at pH 6.5 when compared with pH 7.4. In additional experiments with the perfused rat hindquarter, rates of glyconeogenesis were shown to be highly correlated with proportion of FT muscle fibers in a muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


1988 ◽  
Vol 36 (6) ◽  
pp. 633-637 ◽  
Author(s):  
D A Riley ◽  
S Ellis ◽  
J L Bain

The size, distribution, and content of catalase-reactive microperoxisomes were studied cytochemically in slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG), and fast-twitch glycolytic (FG) fibers of soleus and extensor digitorum longus (EDL) rat muscles. Fiber types were classified on the basis of mitochondrial content and distribution, Z-band widths, and myofibril size and shape. Microperoxisomes were generally located between myofibrils at the I-bands. The absence of crystalloid inclusions prevented positive identification of microperoxisomes in nonreacted and aminotriazole-inhibited muscles. EDL and soleus SO fibers possessed the largest microperoxisomes, whereas FOG and FG fibers of the EDL contained small- to medium-sized microperoxisomes. Comparing either microperoxisome number per muscle fiber area or microperoxisome area per fiber area revealed significant differences between fiber types with this ranking: soleus SO greater than EDL SO greater than EDL FOG greater than EDL FG. The present observations demonstrate that the content of catalase-positive microperoxisomes is greatest in the oxidative muscle fiber types. These cytochemical findings account for the higher catalase activity in homogenates of soleus muscles as compared to that of EDL muscles, because the soleus contains more oxidative fibers than EDL.


1976 ◽  
Vol 230 (6) ◽  
pp. 1644-1649 ◽  
Author(s):  
IR Wendt ◽  
JB Chapman

Recovery metabolism of fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles of the rat has been investigated using fluorometric monitoring of reduction of nicotinamide adenine dinucleotide (NAD). In both EDL and SOL, groups of twitch contractions produced a decrease in fluorescence (oxidation of NADH) which returned to the resting base line after contraction ceased. These responses proceeded more quickly in EDL than SOL and were abolished by anoxia. A 1-s tetanus of SOL produced an initial reduction which could be abolished with iodoacetate followed by a prolonged oxidation which could be blocked by anoxia. The fluorescence of EDL was decreased immediately following a 1-s tetanus but then rapidly increased well beyond the resting level of reduction and persisted throughout the recovery period. This reduction was largely depressed by iodoacetate. The results indicate marked differences in the recovery metabolism of these muscles, consistent with predominantly mitochondrial oxidative activity in the slow-twitch muscles and predominantly glycolytic activity in the fast-twitch muscles.


1996 ◽  
Vol 43 (4) ◽  
pp. 693-700 ◽  
Author(s):  
J Moraczewski ◽  
E Piekarska ◽  
M Zimowska ◽  
M Sobolewska

Calpains--non-lysosomal intracellular calcium-activated neutral proteinases, form a family consisting of several distinct members. Two of the isoenzymes: mu (calpain I) and m (calpain II) responded differently to the injury during complete regeneration of Extensor digitorum longus (EDL) muscle and partial regeneration of Soleus muscle. In the crushed EDL the level of m-calpain on the 3rd and 7th day of regeneration was higher than in non-operated muscles, whereas the activity of this calpain in injured Soleus decreased. The level of mu-calpain in EDL oscillated irregularly during regeneration whereas in Soleus of both injured and contralateral muscles its level rapidly rose. Our results support the hypothesis that m-calpain is involved in the process of fusion of myogenic cells whereas mu-calpain plays a significant but indirect role in muscle regeneration.


1993 ◽  
Vol 74 (5) ◽  
pp. 2161-2165 ◽  
Author(s):  
M. E. Tischler ◽  
E. J. Henriksen ◽  
K. A. Munoz ◽  
C. S. Stump ◽  
C. R. Woodman ◽  
...  

Our knowledge of the effects of unweighting on skeletal muscle of juvenile rapidly growing rats has been obtained entirely by using hindlimb-suspension models. No spaceflight data on juvenile animals are available to validate these models of simulated weightlessness. Therefore, eight 26-day-old female Sprague-Dawley albino rats were exposed to 5.4 days of weightlessness aboard the space shuttle Discovery (mission STS-48, September 1991). An asynchronous ground control experiment mimicked the flight cage condition, ambient shuttle temperatures, and mission duration for a second group of rats. A third group of animals underwent hindlimb suspension for 5.4 days at ambient temperatures. Although all groups consumed food at a similar rate, flight animals gained a greater percentage of body mass per day (P < 0.05). Mass and protein data showed weight-bearing hindlimb muscles were most affected, with atrophy of the soleus and reduced growth of the plantaris and gastrocnemius in both the flight and suspended animals. In contrast, the non-weight-bearing extensor digitorum longus and tibialis anterior muscles grew normally. Earlier suspension studies showed that the soleus develops an increased sensitivity to insulin during unweighting atrophy, particularly for the uptake of 2-[1,2–3H]deoxyglucose. Therefore, this characteristic was studied in isolated muscles within 2 h after cessation of spaceflight or suspension. Insulin increased uptake 2.5- and 2.7-fold in soleus of flight and suspended animals, respectively, whereas it increased only 1.6-fold in control animals. In contrast, the effect of insulin was similar among the three groups for the extensor digitorum longus, which provides a control for potential systemic differences in the animals.


1996 ◽  
Vol 270 (3) ◽  
pp. H817-H826 ◽  
Author(s):  
H. Bolukoglu ◽  
G. W. Goodwin ◽  
P. H. Guthrie ◽  
S. G. Carmical ◽  
T. M. Chen ◽  
...  

The acute adaptation of myocardial glucose metabolism in response to low-flow ischemia and reperfusion was investigated in isolated working rat hearts perfused with bicarbonate saline containing glucose (10 mM) and insulin (40 microU/ml). Reversible low-flow ischemia was induced by reducing coronary perfusion pressure from 100 to 35 cmH2O. Tritiated glucose was used to assess rates of glucose transport and phosphorylation, flux from glucose to pyruvate, and oxidation of exogenous glucose. Rates of glycogen synthesis and glycolysis were also assessed. With ischemia, cardiac power decreased by more than two-thirds. Rates of glucose uptake and flux from glucose to pyruvate remained unchanged, while glucose oxidation declined by 61%. Rates of lactate release more than doubled, and fractional enrichment of glycogen remained the same. During reperfusion, glucose oxidation returned to the preischemic values. When isoproterenol was added during ischemia, glucose uptake increased, glycogen decreased, and lactate release increased. No effect was seen with pacing. We conclude that during low-flow ischemia and with glucose as the only exogenous substrate, net glucose uptake remains unchanged. There is a reversible redirection between glycolysis and glucose oxidation, while glycogen synthesis continues during ischemia and is enhanced with reperfusion.


1987 ◽  
Vol 253 (3) ◽  
pp. C426-C432 ◽  
Author(s):  
D. M. Whitlock ◽  
R. L. Terjung

Rat slow-twitch muscle, in contrast to fast-twitch muscle, maintains its ATP content near normal during intense stimulation conditions that produce rapid fatigue. An extensive depletion of adenine nucleotide content by the deamination of AMP to IMP + NH3, typical of fast-twitch muscle, does not occur. We evaluated whether this response of slow-twitch muscle could be simply due to failure of synaptic transmission or related to cellular conditions influencing enzyme activity. Stimulation of soleus muscles in situ via the nerve or directly in the presence of curare at 120 tetani/min for 3 min resulted in extensive fatigue but normal ATP contents. Thus the lack of ATP depletion must be related to cellular events distal to neuromuscular transmission. Even nerve and direct muscle stimulation (with curare) during ischemia did not cause a large depletion of ATP or a large elevation of lactate content (12.0 +/- 0.7 mumol/g), even though the decline in tension was essentially complete. However, if the same tension decline during ischemia was prolonged by stimulating for 10 min at 12 tetani/min a large decrease in ATP (2.24 +/- 0.09 mumol/g) and increase in IMP (2.47 +/- 0.16 mumol/g) and lactate (30.4 +/- 2.0 mumol/g) content occurred. Thus adenine nucleotide deamination to IMP can occur in slow-twitch muscle during specific contraction conditions. The cellular events leading to the activation of AMP deaminase require an intense contraction condition and may be related to acidosis caused by a high lactate content.


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