scholarly journals Physiological glucocorticoid levels regulate glutamine and insulin-mediated glucose metabolism in skeletal muscle of the rat. Studies with RU 486 (mifepristone)

1991 ◽  
Vol 274 (1) ◽  
pp. 187-192 ◽  
Author(s):  
B Leighton ◽  
M Parry-Billings ◽  
G Dimitriadis ◽  
J Bond ◽  
E A Newsholme ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Plasma Glucose ◽  
Dark Period ◽  
Feeding Activity ◽  
Glycogen Synthesis ◽  
Glutamine Metabolism ◽  
Ru 486

This study examined the effects of antagonism of the peak level of glucocorticoids in vivo, which occurs as rats enter the feeding/activity (dark) period on glucose and glutamine metabolism in incubated isolated rat soleus muscle preparations. Thus the rats were treated with the potent glucocorticoid antagonist RU 486 2 h before and 1 and 2 h into the dark period. Both the content of glutamine in skeletal muscle in vivo and plasma glucose and glutamine concentrations were elevated midway through the dark period, compared with the beginning of the period. RU 486 prevented the increases in plasma glucose and glutamine and caused a significant decrease in both the rate of release of glutamine in soleus muscle in vitro and the content of glutamine in gastrocnemius muscle. The sensitivity of soleus muscle to insulin in vitro is markedly decreased when isolated midway through the dark period (i.e. at 03:00 h) [Leighton, Kowalchuk, Challiss & Newsholme (1988) Am. J. Physiol. 255, E41-E45]. We now show that the concentrations of insulin required to stimulate lactate formation and glycogen synthesis half-maximally were 95 and 250 muunits/ml respectively, and treatment of rats with RU 486 decreased these values to 55 and 90 muunits of insulin/ml respectively. Thus antagonism of the action of the normal circadian rise in the level of glucocorticoids in rats reverses insulin insensitivity in soleus muscles in vitro.

scholarly journals Effects of prolonged elevation of plasma adrenaline concentration in vivo on insulin-sensitivity in soleus muscle of the rat

1987 ◽  
Vol 244 (3) ◽  
pp. 655-660 ◽  
Author(s):  
L Budohoski ◽  
R A Challiss ◽  
A Dubaniewicz ◽  
H Kaciuba-Usciłko ◽  
B Leighton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Biochemical Basis ◽  
Plasma Adrenaline ◽  
Skeletal Muscle Insulin Sensitivity

1. Prolonged elevation of the plasma adrenaline concentration was produced in rats by implantation of adrenaline-releasing retard-tablets. With this technique, a hyperadrenalinaemic state is maintained for at least 5 days. 2. At 6 h after implantation of the retard-tablet it was found that plasma glucose and fatty acid concentrations increased and insulin concentration decreased compared with values obtained from placebo-tablet-implanted rats. Administration of a subcutaneous glucose load demonstrated an impaired glucose tolerance in vivo, and incubation of soleus muscle strips from 6 h-hyperadrenalinaemic rats in vitro demonstrated a decreased sensitivity of the rates of glycolysis and glucose transport to insulin. 3. The sensitivities of the rates of glycolysis, glucose transport and glycogen synthesis to insulin were determined for the incubated soleus muscle preparation isolated from animals after 48 h, 72 h and 120 h duration of hyperadrenalinaemia. At 48 h after retard-tablet implantation, the sensitivity of the processes of glucose transport and glycolysis was decreased; at 72 h, the insulin-sensitivities of the rates of glycolysis and glucose transport in skeletal muscle were similar to those determined for control animals; at 120 h, however, the sensitivities of the processes of glucose transport and glycolysis were both statistically significantly increased. In contrast, no changes in the sensitivity of the process of glycogen synthesis were observed at any of the time intervals studied. 4. The possible biochemical basis for the observed changes in skeletal-muscle insulin-sensitivity with prolonged hyperadrenalinaemia is discussed.

Glutamine Metabolism in Skeletal Muscle of Glucocorticoid-Treated Rats

1990 ◽  
Vol 79 (2) ◽  
pp. 139-147 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Yasir S. Jamal
Keyword(s):  
Skeletal Muscle ◽  
Exchange Rates ◽  
Skeletal Muscles ◽  
Plasma Concentrations ◽  
Maximal Activity ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Concentration Difference

1. The effect of dexamethasone (30 μg day−-1 100 g−-1 body weight) on the regulation of glutamine metabolism was studied in skeletal muscles of rats after 9 days of treatment. 2. Dexamethasone resulted in negative nitrogen balance, and produced increases in the plasma concentrations of alanine (23.4%) and insulin (158%) but a decrease in the plasma concentration of glutamine (28.7%). 3. Dexamethasone treatment increased the rate of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb. 4. Blood flow and arteriovenous concentration difference measurements across the hindlimb showed an increase in the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone-treated rats compared with corresponding controls. 5. Dexamethasone treatment produced significant decreases in the concentrations of skeletal muscle glutamine (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%), pyruvate (45.9%), ammonia (43.3%) and inosine 5′-phosphate (141.8%) were increased. 6. The maximal activity of glutamine synthetase was increased (21–34%), but there was no change in that of glutaminase, in muscles of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of release of both glutamine and alanine from skeletal muscle of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.

scholarly journals In Vivo Bioluminescence Imaging – A Suitable Method to Track Mesenchymal Stromal Cells in a Skeletal Muscle Trauma§

2015 ◽  
Vol 9 (1) ◽  
pp. 262-269 ◽  
Author(s):  
K. Strohschein ◽  
P Radojewski ◽  
T. Winkler ◽  
G.N. Duda ◽  
C Perka ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mesenchymal Stromal Cells ◽  
Soleus Muscle ◽  
Stromal Cells ◽  
Bioluminescence Imaging ◽  
Suitable Method ◽  
Cellular Kinetics ◽  
Muscle Trauma

Cell-based therapies have emerged during the last decade in various clinical fields. Especially mesenchymal stromal cells (MSCs) have been used in pre-clinical and clinical applications in cardiovascular, neurodegenerative and musculoskeletal disorders. In order to validate survival and viability as well as possible engraftment of MSCs into the host tissue a live cell imaging technique is needed that allows non-invasive, temporal imaging of cellular kinetics as well as evaluation of cell viability after transplantation. In this study we used luciferase-based bioluminescence imaging (BLI) to investigate the survival of autologous MSCs transplanted into a severely crushed soleus muscle of the rats. Furthermore we compared local as well as intra-arterial (i.a.) administration of cells and analyzed if luciferase transduced MSCs depict the same characteristics in vitro as non-transduced MSCs. We could show that transduction of MSCs does not alter their in vitro characteristics, thus, transduced MSCs display the same differentiation, proliferation and migration capacity as non-transduced cells. Using BLI we could track MSCs transplanted into a crushed soleus muscle until day 7 irrespective of local or i.a. application. Hence, our study proves that luciferase-based BLI is a suitable method for in vivo tracking of MSCs in skeletal muscle trauma in rats.

scholarly journals The role of the sensory peptide calcitonin-gene-related peptide(s) in skeletal muscle carbohydrate metabolism: effects of capsaicin and resiniferatoxin

1995 ◽  
Vol 307 (3) ◽  
pp. 707-712 ◽  
Author(s):  
B Leighton ◽  
E A Foot
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Calcitonin Gene Related Peptide ◽  
Sensory Nerves ◽  
Muscle Fibres ◽  
Related Peptide ◽  
Calcitonin Gene

1. The content of calcitonin-gene-related-peptide-like immunoreactivity (CGRP-LI) in various rat muscles was measured. Starvation for 24 h did not affect the content of CGRP-LI in these muscles, except for a decreased level in the starved-rat diaphragm. Higher contents of CGRP-LI were observed in well-vascularized muscles. 2. Capsaicin (at 1, 10 and 100 microM) inhibited insulin-stimulated rates of glycogen synthesis in isolated stripped incubated soleus muscle preparations by a mechanism independent of catecholamine release, since the effects of capsaicin were not altered by the beta-adrenoreceptor antagonist DL-propranolol. 3. Resiniferatoxin (10 nM), which is a potent capsaicin agonist, also significantly inhibited the insulin-stimulated rate of glycogen synthesis. Furthermore, the concentration of resiniferatoxin required to inhibit glycogen synthesis was 100 times less than the concentration of capsaicin needed for the same effect. 4. Capsaicin (10 microM) decreased the content of CGRP-LI in isolated stripped incubated soleus muscle preparations by about 40%. 5. Neonatal treatment of rats with capsaicin, which causes de-afferentation of some sensory nerves such, we hypothesize, that CGRP can no longer be released to counteract the effects of insulin in vivo, caused increased rates of glycogen synthesis and increased glycogen content in stripped soleus muscle preparations in vitro when muscles were isolated from the adult rats. 6. These findings support the hypothesis that capsaicin and resiniferatoxin elicit an excitatory response on sensory nerves in skeletal muscle in vitro to cause the efferent release of CGRP. Consequently, CGRP is delivered to skeletal muscle fibres to inhibit insulin-stimulated glycogen synthesis. The role of CGRP in recovery of blood glucose levels during hypoglycaemia is discussed.

Effects of Insulin on Glucose Metabolism in Skeletal Muscle from Septic and Endotoxaemic Rats

1989 ◽  
Vol 77 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Brendan Leighton ◽  
George D. Dimitriadis ◽  
Mark Parry-Billings ◽  
Jane Bond ◽  
Paulo R. L. de Vasconcelos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Dependent Manner ◽  
H 26 ◽  
Lactate Formation ◽  
Dose Dependent

1. The effects of non-lethal bacteraemia or endotoxaemia on insulin-stimulated glucose metabolism were studied in isolated, incubated soleus muscle of rats after 24 and 48 h. 2. The insulin-stimulated rates of lactate formation and glycogen synthesis were similar in muscles isolated from control and bacteraemic rats. 3. Endotoxaemia increased the rates of lactate formation, at all levels of insulin, both at 24 h (∼ 32%) and 48 h (∼ 26%). Endotoxaemia did not alter the sensitivity of glycolysis to insulin. 4. Endotoxaemia decreased the rates of glycogen synthesis at all concentrations of insulin both at 24 h (∼ 39%) and 48 h (∼ 23%). 5. The increase in the rate of glycolysis was related in a dose-dependent manner to the amount of endotoxin given to the animals. 6. Endotoxaemia decreased plasma tri-iodothyronine levels (41%). However, the effects of endotoxaemia (48 h) on glucose metabolism in muscle are similar to those caused by hyperthyroidism. In hypothyroid rats, endotoxin administration increased the rates of glycolysis in muscle in vitro. 7. It is concluded that there are enhanced basal and insulin-stimulated rates of glycolysis in soleus muscle from endotoxaemic rats. This may be due to both increased glucose transport and decreased glycogen synthesis.

Regulation of phosphatidylinositol 3-kinase by insulin in rat skeletal muscle

1993 ◽  
Vol 265 (5) ◽  
pp. E736-E742 ◽  
Author(s):  
K. S. Chen ◽  
J. C. Friel ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Receptor Protein ◽  
Mammalian Skeletal Muscle ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

The presence of phosphatidylinositol 3-kinase (PI 3-kinase) in mammalian skeletal muscle and its response to insulin stimulation were investigated. PI kinase, immunoprecipitated from rat soleus muscle with antibodies directed toward its 85-kDa subunit phosphorylated PI, phosphatidylinositol 4-phosphate [PI(4)P], and phosphatidylinositol 4,5,-bisphosphate [PI(4,5)P2] to yield phosphatidylinositol 3-phosphate [PI(3)P], phosphatidylinositol 3,4,-bisphosphate, and phosphatidylinositol trisphosphate in vitro. PI 3-kinase activity was also immunoprecipitated with antiphosphotyrosine [alpha-Tyr(P)] antibodies and with antibodies raised against IRS-1, a substrate of the insulin receptor protein tyrosine kinase that associates with and activates PI 3-kinase. Incubation of the soleus with insulin in vitro, or injection of insulin into rats in vivo, produced three- to fivefold increases in alpha-Tyr(P)- and alpha-IRS-1-immunoprecipitable PI 3-kinase activity. In nonstimulated soleus muscle, PI 3-kinase activity immunoprecipitated with alpha-IRS-1 or with alpha-Tyr(P) antibodies was evenly distributed between particulate (200,000-g pellet) and soluble fractions. Insulin treatment increased immunoprecipitable PI 5-kinase activity in both fractions, but the increase in alpha-Tyr-(P)-precipitable activity was greater in the particulate fraction, whereas the increase in alpha-IRS-1-precipitable activity was greater in the soluble fraction. In intact soleus muscles incubated with 32PO4, insulin increased the labeling of PI(3)P but did not affect the labeling of PI(4)P or PI(4,5)P2. Activation of PI 3-kinase by insulin was unaffected by prior denervation of the muscle, a manipulation that has been shown to cause both insulin resistance and hypersensitivity in muscles, depending on the parameter measured.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sensitivity of the soleus muscle to insulin in resting and exercising rats with experimental hypo- and hyper-thyroidism

1989 ◽  
Vol 263 (1) ◽  
pp. 243-247 ◽  
Author(s):  
A Dubaniewicz ◽  
H Kaciuba-Usciłko ◽  
K Nazar ◽  
L Budohoski
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Soleus Muscle ◽  
Interactive Effect ◽  
Glycogen Synthesis ◽  
Subcutaneous Administration ◽  
Lactate Production ◽  
Glucose Injection ◽  
Lactate Formation

1. The effects of hypothyroidism (caused by surgical thyroidectomy followed by treatment for 1 month with propylthiouracil) and of hyperthyroidism [induced by subcutaneous administration of L-tri-iodothyronine (T3)] on glucose tolerance and skeletal-muscle sensitivity to insulin were examined in rats. Glucose tolerance was estimated during 2 h after subcutaneous glucose injection (1 g/kg body wt.). The sensitivity of the soleus muscle to insulin was studied in vitro in sedentary and acutely exercised animals. 2. Glucose tolerance was impaired in both hypothyroid and hyperthyroid rats in comparison with euthyroid controls. 3. In the soleus muscle, responsiveness of the rate of lactate formation to insulin was abolished in hypothyroid rats, whereas the sensitivity of the rate of glycogen synthesis to insulin was unchanged. In hyperthyroid animals, opposite changes were found, i.e. responsiveness of the rate of glycogen synthesis was inhibited and the sensitivity of the rate of lactate production did not differ from that in control sedentary rats. 4. A single bout of exercise for 30 min potentiated the stimulatory effect of insulin on lactate formation in hyperthyroid rats and on glycogen synthesis in hypothyroid animals. 5. The data suggest that thyroid hormones exert an interactive effect with insulin in skeletal muscle. This is likely to be at the post-receptor level, inhibiting the effect of insulin on glycogen synthesis and stimulating oxidative glucose utilization.

scholarly journals DHA/EPA Improves GLUT4 Translocation, Glycogen Synthesis and Aerobic Glycolysis in Skeletal Muscle of db/db Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 591-591
Author(s):  
Haoyu Li ◽  
Wenqiao Wang ◽  
Pan Zhuang ◽  
Jingjing Jiao ◽  
Yu Zhang
Keyword(s):  
Skeletal Muscle ◽  
Aerobic Glycolysis ◽  
Control Diet ◽  
Glycogen Synthesis ◽  
Glucose Consumption ◽  
Underlying Mechanism ◽  
C2c12 Myotubes ◽  
Glut4 Translocation

Abstract Objectives The aim of this study was to investigate the effects of DHA and EPA on glucose metabolism including glucose uptake and disposal in skeletal muscle and C2C12 myotubes. Methods Four-week-old db/db diabetic mice were fed with control diet enriched with DHA/EPA (purity > 99%,  1% wt/wt) for 10 weeks. To further explore the underlying mechanism, C2C12 myotubes were induced insulin resistance by palmitate and treated with 25 and 50 μM DHA/EPA for 24 h after differentiation. Results The untargeted metabolome of skeletal muscle showed BCAAs and other metabolites associated with glycolysis and TCA cycle were altered by DHA/EPA treatment. Further detections revealed DHA/EPA treatment promoted the translocation of GLUT4 via increasing Rab8a and SNAP23 expression, and enhanced the activity of GS and PDH. In vitro, the glucose consumption was improved coupled with promoted Rab8a or SNAP23, and GS and PDH were also activated under DHA/EPA intervention increased glucose consumption via promoted Rab8a and SNAP23. The GS and PDH were also activated, which were in line with the results in vivo. Conclusions Long-term intake of DHA and EPA may have a protective effect on diabetes through promoted GLUT4 translocation, glycogen synthesis and aerobic glycolysis in skeletal muscle. Funding Sources This work was supported by the National Natural Science Foundation of China (grant number 81773419 and 81300309), Chinese Institute of Nutrition DSM Research Fund (grant number CNS-DSM-2017–035), China National Program for Support of Top-notch Young Professionals and China Postdoctoral Science Foundation (grant number 2020M681869).

Relative metabolic utilization of in situ rabbit soleus muscle: thermistor-based measurements and model

2000 ◽  
Vol 203 (23) ◽  
pp. 3667-3674
Author(s):  
K.J. Gustafson ◽  
G.D. Egrie ◽  
S.H. Reichenbach
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Muscle Length ◽  
Multiple Linear Regression Model ◽  
Active Tension ◽  
Contraction Duration ◽  
Continuous Power

Electrically conditioned skeletal muscle can provide the continuous power source for cardiac assistance devices. Optimization of the available sustained power from in vivo skeletal muscle requires knowledge of its metabolic utilization and constraints. A thermistor-based technique has been developed to measure temperature changes and to provide a relative estimate for metabolic utilization of in situ rabbit soleus muscle. The relative thermistor response, active tension and muscle displacement were measured during cyclic isometric and isotonic contractions across a range of muscle tensions and contraction durations. The thermistor response demonstrated linear relationships versus both contraction duration at a fixed muscle length and active tension at a fixed contraction duration (r(2)=0.90+/−0.14 and 0.70+/−0.21, respectively; means +/− s.d.). A multiple linear regression model was developed to predict normalized thermistor response, DeltaT, across a range of conditions. Significant model variables were identified using a backward stepwise regression procedure. The relationships for the in situ muscles were qualitatively similar to those reported for mammalian in vitro muscle fiber preparations. The model had the form DeltaT=C+at(c)F+bW, where the constant C, and coefficients for the contraction duration t(c) (ms), normalized active tension F and normalized net work W were C=−1.00 (P<0.001), a=5.97 (P<0.001) and b=2.12 (P<0.001).

scholarly journals Mechanism of Attenuation of Skeletal Muscle Atrophy by Zinc-α2-Glycoprotein

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4696-4704 ◽  
Author(s):  
Steven T. Russell ◽  
Michael J. Tisdale
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Mammalian Target Of Rapamycin ◽  
Ring Finger ◽  
Initiation Factor ◽  
Skeletal Muscle Atrophy ◽  
Intracellular Camp

The mechanism by which the adipokine zinc-α2-glycoprotein (ZAG) increases the mass of gastrocnemius, but not soleus muscle of diabetic mice, has been evaluated both in vivo and in vitro. There was an increased phosphorylation of both double-stranded RNA-dependent protein kinase and its substrate, eukaryotic initiation factor-2α, which was attenuated by about two-thirds in gastrocnemius but not soleus muscle of ob/ob mice treated with ZAG (50 μg, iv daily) for 5 d. ZAG also reduced the expression of the phospho forms of p38MAPK and phospholipase A2, as well as expression of the ubiquitin ligases (E3) muscle atrophy F-box/atrogin-1 and muscle RING finger protein, and the increased activity of both caspase-3 and casapse-8 to values found in nonobese controls. ZAG also increased the levels of phospho serine-threonine kinase and mammalian target of rapamycin in gastrocnemius muscle and reduced the phosphorylation of insulin receptor substrate-1 (Ser307) associated with insulin resistance. Similar changes were seen with ZAG when murine myotubes were incubated with high glucose concentrations (10 and 25 mm), showing that the effect of ZAG was direct. ZAG produced an increase in cAMP in murine myotubes, and the effects of ZAG on protein synthesis and degradation in vitro could be replicated by dibutyryl cAMP. ZAG increased cAMP levels of gastrocnemius but not soleus muscle. These results suggest that protein accretion in skeletal muscle in response to ZAG may be due to changes in intracellular cAMP and also that ZAG may have a therapeutic application in the treatment of muscle wasting conditions.

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