Acute alcohol administration attenuates insulin-mediated glucose use by skeletal muscle

1994 ◽  
Vol 267 (6) ◽  
pp. E886-E891 ◽  
Author(s):  
Z. Spolarics ◽  
G. J. Bagby ◽  
P. H. Pekala ◽  
C. Dobrescu ◽  
N. Skrepnik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Alcohol Intake ◽  
Glucose Utilization ◽  
Inhibitory Effect ◽  
Alcohol Administration ◽  
Ethanol Infusion ◽  
Glucose Recycling ◽  
The Brain ◽  
Fasted Rats

The aim of the present work was to test the effect of acute in vivo alcohol administration (180–190 mg/dl plasma for 3 h) on glucose utilization by tissues under basal conditions or after a hyperinsulinemic (100–130 microU/ml) euglycemic clamp in fasted rats. In vivo glucose use by individual tissues was assessed by the tracer 2-deoxy-D-glucose technique. Alcohol administration to saline-infused rats markedly inhibited glucose use by skeletal muscles, including the soleus, white and red quadriceps, and gastrocnemius, as well as by the heart. Ethanol infusion, however, had no effect on glucose use by the diaphragm, lung, liver, skin, ileum, brain, and adipose tissue. The insulin-stimulated glucose use was also inhibited by alcohol selectively in the muscles, with no effect on other tissues tested, except a moderate inhibition in the brain. Ethanol inhibited muscle glucose use by an average of approximately 50% under both basal and insulin-stimulated conditions. However, because insulin treatment more than doubled basal glucose use by these muscles, the 50% inhibition by ethanol treatment represents a greater inhibition of absolute glucose use under insulin-stimulated rather than under basal conditions. Our data demonstrate that acute alcohol intake attenuates basal and hormone-induced glucose utilization in a tissue-specific fashion. The inhibitory effect of alcohol on skeletal muscle glucose use could contribute to the previously observed decreased glucose recycling in humans after acute alcohol intake.

scholarly journals An investigation of arterial insufficiency in the rat hindlimb Correlation of skeletal muscle bloodflow and glucose utilization in vivo

1986 ◽  
Vol 240 (2) ◽  
pp. 395-401 ◽  
Author(s):  
R A Challiss ◽  
D J Hayes ◽  
G K Radda
Keyword(s):  
Skeletal Muscle ◽  
Sciatic Nerve ◽  
Glucose Uptake ◽  
Nerve Stimulation ◽  
Linear Correlation ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Artery Ligation ◽  
Sciatic Nerve Stimulation

Muscle bloodflow and the rate of glucose uptake and phosphorylation were measured in vivo in rats 7 days after unilateral femoral artery ligation and section. Bloodflow was determined by using radiolabelled microspheres. At rest, bloodflow to the gastrocnemius, plantaris and soleus muscles of the ligated limb was similar to their respective mean contralateral control values; however, bilateral sciatic nerve stimulation at 1 Hz caused a less pronounced hyperaemic response in the muscles of the ligated limb, being 59, 63 and 49% of their mean control values in the gastrocnemius, plantaris and soleus muscles respectively. The rate of glucose utilization was determined by using the 2-deoxy[3H]glucose method [Ferré, Leturque, Burnol, Penicaud & Girard (1985) Biochem. J. 228, 103-110]. At rest, the rate of glucose uptake and phosphorylation was statistically significantly increased in the gastrocnemius and soleus muscles of the ligated limb, being 126 and 140% of the mean control values respectively. Bilateral sciatic nerve stimulation at 1 Hz caused a 3-5-fold increase in the rate of glucose utilization by the ligated and contralateral control limbs; furthermore, the rate of glucose utilization was significantly increased in the muscles of the ligated limb, being 140, 129 and 207% of their mean control values respectively. For the range of bloodflow to normally perfused skeletal muscle at rest or during isometric contraction determined in the present study, a linear correlation between the rate of glucose utilization and bloodflow can be demonstrated. Applying similar methods of regression analysis to glucose utilization and bloodflow to muscles of the ligated limb reveals a similar linear correlation. However, the rate of glucose utilization at a given bloodflow is increased in muscles of the ligated limb, indicating an adaptation of skeletal muscle to hypoperfusion.

Enhancement of maximal thermogenesis by reducing endogenous adenosine activity in the rat

1990 ◽  
Vol 68 (2) ◽  
pp. 580-585 ◽  
Author(s):  
L. C. Wang ◽  
T. F. Lee
Keyword(s):  
Skeletal Muscle ◽  
Cold Exposure ◽  
Adenosine Receptor ◽  
Glucose Utilization ◽  
Cold Resistance ◽  
Atp Hydrolysis ◽  
A1 Receptor ◽  
Thermogenic Capacity

Adenosine has been shown in vitro to be a potent antilipolytic agent and an inhibitor of insulin-stimulated glucose utilization in skeletal muscle. To test whether endogenously produced adenosine (e.g., from ATP hydrolysis) shares these deleterious effects on substrate mobilization and utilization and thus limits maximum thermogenesis in vivo, adenosine deaminase (converts adenosine to inosine) was given to rats 15 min before cold exposure. Significant (P less than 0.05) increases in thermogenesis were observed under both well-fed (100 units/kg ip) and food-rationed (200 units/kg ip) states. Significant (P less than 0.05) increases in thermogenesis and cold resistance were also observed after pretreatment with selective adenosine receptor antagonists [8-cyclopentyltheophylline (1 microgram/kg ip) greater than 1,3-dipropyl-8-p-sulfophenylxanthine (1.25 mg/kg ip) greater than aminophylline (18.7 mg/kg ip)], indicating an A1-receptor-mediated effect. These results indicate that endogenously released adenosine can indeed attenuate the thermogenic capacity in severe cold and that adenosine antagonists, especially those selective for A1-receptor, are useful in improving cold resistance under varying nutritional states.

scholarly journals Skeletal Muscle-Selective Knockout of LKB1 Increases Insulin Sensitivity, Improves Glucose Homeostasis, and Decreases TRB3

2006 ◽  
Vol 26 (22) ◽  
pp. 8217-8227 ◽  
Author(s):  
Ho-Jin Koh ◽  
David E. Arnolds ◽  
Nobuharu Fujii ◽  
Thien T. Tran ◽  
Marc J. Rogers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Glucose Utilization ◽  
Cell Metabolism ◽  
Negative Regulator ◽  
Akt Inhibitor ◽  
Akt Phosphorylation ◽  
Energy Sensing

ABSTRACT LKB1 is a tumor suppressor that may also be fundamental to cell metabolism, since LKB1 phosphorylates and activates the energy sensing enzyme AMPK. We generated muscle-specific LKB1 knockout (MLKB1KO) mice, and surprisingly, found that a lack of LKB1 in skeletal muscle enhanced insulin sensitivity, as evidenced by decreased fasting glucose and insulin concentrations, improved glucose tolerance, increased muscle glucose uptake in vivo, and increased glucose utilization during a hyperinsulinemic-euglycemic clamp. MLKB1KO mice had increased insulin-stimulated Akt phosphorylation and a >80% decrease in muscle expression of TRB3, a recently identified Akt inhibitor. Akt/TRB3 binding was present in skeletal muscle, and overexpression of TRB3 in C2C12 myoblasts significantly reduced Akt phosphorylation. These results demonstrate that skeletal muscle LKB1 is a negative regulator of insulin sensitivity and glucose homeostasis. LKB1-mediated TRB3 expression provides a novel link between LKB1 and Akt, critical kinases involved in both tumor genesis and cell metabolism.

scholarly journals Effects of potassium deficiency on growth and protein synthesis in skeletal muscle and the heart of rats

1989 ◽  
Vol 62 (2) ◽  
pp. 269-284 ◽  
Author(s):  
Inge Dôrup ◽  
Torben Clausen
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Control Level ◽  
Inhibitory Effect ◽  
Potassium Deficiency ◽  
Skeletal Muscle Protein ◽  
K Deficiency

The effects of potassium deficiency on growth, K content and protein synthesis have been compared in 4–13-week-old rats. When maintained on K-deficient fodder (1 mmol/kg) rats ceased to grow within a few days, and the incorporation of [3H]leucine into skeletal muscle protein in vivo was reduced by 28–38%. Pair-feeding experiments showed that this inhibition was not due to reduced energy intake. Following 14 d on K-deficient fodder, there was a further reduction (39–56 %) in the incorporation of [3H]leucine into skeletal muscle protein, whereas the incorporation into plasma, heart and liver proteins was not affected. The accumulation of the non-metabolized amino acid α-aminoisobutyric acid in the heart and skeletal muscles was not reduced. The inhibitory effect of K deficiency on 3H-labelling of muscle protein was seen following intraperitoneal (10–240 min) as well as intravenous (10 min) injection of [3H]leucine. In addition, the incorporation of [3H]phenylalanine into skeletal muscle protein was reduced in K-depleted animals. Following acute K repletion in vivo leading to complete normalization of muscle K content, the incorporation of [3H]leucine into muscle protein showed no increase within 2 h, but reached 76 and 104% of the control level within 24 and 72 h respectively. This was associated with a rapid initial weight gain, but normal body-weight was not reached until after 7 weeks of K repletion. Following 7 d on K-deficient fodder the inhibition of growth and protein synthesis was closely correlated with the K content of the fodder (1–40 mmol/kg) and significant already at modest reductions in muscle K content. In vitro experiments with soleus muscle showed a linear relationship between the incorporation of [3H]leucine into muscle protein and K content, but the sensitivity to cellular K deficiency induced in vitro was much less pronounced than that induced in vivo. Thus, in soleus and extensor digitorum longus (EDL) muscles prepared from K-deficient rats, the incorporation of [3H]leucine was reduced by 30 and 47 % respectively. This defect was completely restored by 24 h K repletion in vivo. It is concluded that in the intact organism protein synthesis and growth are very sensitive to dietary K deficiency and that this can only partly be accounted for by the reduction in cellular K content per se. The observations emphasize the need for adequate K supplies to ensure optimum utilization of food elements for protein synthesis and growth.

Kanamycin Inhibits Cochlear-Renal ODC in Neonatal Rats

1992 ◽  
Vol 107 (4) ◽  
pp. 501-510 ◽  
Author(s):  
Andrew T. Lyos ◽  
William E. Winter ◽  
Charles M. Henley
Keyword(s):  
Organ Of Corti ◽  
Lateral Wall ◽  
Inhibitory Effect ◽  
Polyamine Biosynthesis ◽  
Key Enzyme ◽  
Old Rats ◽  
In Vivo Effects ◽  
The Brain

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is important in development and regeneration. We hypothesize that aminoglycoside inhibition of ODC mediates developmental hypersensitivity to aminoglycoside ototoxicity. Kanamycin effects on ODC activity (decarboxylation of ornithine) in vitro were determined in the postmitochondriai fraction of cochlear and renal homogenates from 11-day-old rats. Kanamycin inhibited cochlear and renal ODC by an uncompetitive mechanism. For the cochlear enzyme, the inhibitor constant (Ki) for kanamycin was 99 ± 25 (μmol/L; for the renal enzyme, the Ki = 1.5 ± 0.1 mmol/L. In vivo effects of kanamycin on cochlear, renal, brain ODC activity were determined in rats treated with kanamycin (400 mg/kg/day, intramuscularly) or saline during postnatal days 11 through 20, the hypersensitive period for ototoxicity. Rats were killed on postnatal days 12,14,16, and 20 and ODC was assayed. Kanamycin significantly inhibited ODC in the lateral wall-organ of Corti and kidney (ANOVA α = 0.05), but had no effect on cochlear nerve and no consistent inhibitory effect in the brain. These results suggest that ODC is a potential target of kanamycin in susceptible tissues and may be a contributing factor in developmental sensitivity to the drug by inhibiting repair and developmental processes mediated by ODC.

Glucose utilization by Kupffer cells, endothelial cells, and granulocytes in endotoxemic rat liver

1991 ◽  
Vol 260 (1) ◽  
pp. G7-G12 ◽  
Author(s):  
K. Meszaros ◽  
J. Bojta ◽  
A. P. Bautista ◽  
C. H. Lang ◽  
J. J. Spitzer
Keyword(s):  
Endothelial Cells ◽  
Kupffer Cells ◽  
Glucose Utilization ◽  
The Body ◽  
Nonparenchymal Cells ◽  
Toxic Metabolites ◽  
Parenchymal Liver ◽  
Cell Fractions ◽  
Fasted Rats

There are several types of glucose-consuming, immunologically active nonparenchymal cells interspersed among the glucose-producing parenchymal liver cells. Combining the in vivo 2-deoxyglucose tracer technique with cell separation methods enabled us to investigate the effect of Escherichia coli endotoxin on the rate of glucose utilization by the nonparenchymal cells. Rats were injected with [14C]deoxyglucose, and intracellular 2-deoxyglucose 6-phosphate was determined in different liver cell fractions. Parenchymal, Kupffer, and endothelial cells as well as polymorphonuclear leukocytes (PMN) were separated from the liver by centrifugal elutriation followed by Ficoll-Hypaque density gradient. The number of PMN obtained from the liver was increased severalfold 3 h after endotoxin and was comparable to the number of Kupffer cells. Glucose utilization by the liver of fasted rats was due predominantly to nonparenchymal cells. Endotoxin enhanced the rate of glucose utilization by Kupffer (6.7-fold) and endothelial (2.7-fold) cells and by the infiltrated hepatic PMN (5.4-fold). Enhanced glucose metabolism of immunologically active cells is part of the hepatic immune response and subserves the antibacterial defense of the body. The activated cells, however, may also have the potential of causing tissue damage by releasing harmful toxic metabolites.

scholarly journals Improved Tetanic Force and Mitochondrial Calcium Homeostasis by Astaxanthin Treatment in Mouse Skeletal Muscle

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 98 ◽  
Author(s):  
Sztretye ◽  
Singlár ◽  
Szabó ◽  
Angyal ◽  
Balogh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calcium Homeostasis ◽  
Inhibitory Effect ◽  
Calcium Transients ◽  
Muscle Performance ◽  
Control Group ◽  
Mitochondrial Calcium ◽  
Tetanic Force

Background: Astaxanthin (AX) a marine carotenoid is a powerful natural antioxidant which protects against oxidative stress and improves muscle performance. Retinol and its derivatives were described to affect lipid and energy metabolism. Up to date, the effects of AX and retinol on excitation-contraction coupling (ECC) in skeletal muscle are poorly described. Methods: 18 C57Bl6 mice were divided into two groups: Control and AX supplemented in rodent chow for 4 weeks (AstaReal A1010). In vivo and in vitro force and intracellular calcium homeostasis was studied. In some experiments acute treatment with retinol was employed. Results: The voltage activation of calcium transients (V50) were investigated in single flexor digitorum brevis isolated fibers under patch clamp and no significant changes were found following AX supplementation. Retinol shifted V50 towards more positive values and decreased the peak F/F0 of the calcium transients. The amplitude of tetani in the extensor digitorum longus was significantly higher in AX than in control group. Lastly, the mitochondrial calcium uptake was found to be less prominent in AX. Conclusion: AX supplementation increases in vitro tetanic force without affecting ECC and exerts a protecting effect on the mitochondria. Retinol treatment has an inhibitory effect on ECC in skeletal muscle.

Lipopolysaccharide and proinflammatory cytokines stimulate interleukin-6 expression in C2C12 myoblasts: role of the Jun NH2-terminal kinase

2003 ◽  
Vol 285 (5) ◽  
pp. R1153-R1164 ◽  
Author(s):  
Robert A. Frost ◽  
Gerald J. Nystrom ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Map Kinases ◽  
Kinase Inhibitors ◽  
Inhibitory Effect ◽  
C2c12 Myoblasts ◽  
Downstream Target ◽  
Tnf Α ◽  
Inflammatory Stimuli

IL-6 is a major inflammatory cytokine that plays a central role in coordinating the acute-phase response to trauma, injury, and infection in vivo. Although IL-6 is synthesized predominantly by macrophages and lymphocytes, skeletal muscle is a newly recognized source of this cytokine. IL-6 from muscle spills into the circulation, and blood-borne IL-6 can be elevated >100-fold due to exercise and injury. The purpose of the present study was to determine whether inflammatory stimuli, such as LPS, TNF-α, and IL-1β, could increase IL-6 expression in skeletal muscle and C2C12 myoblasts. Second, we investigated the role of mitogen-activated protein (MAP) kinases, and the Jun NH2-terminal kinase (JNK) in particular, as a mediator of this response. Intraperitoneal injection of LPS in mice increased the circulating concentration of IL-6 from undetectable levels to 4 ng/ml. LPS also increased IL-6 mRNA 100-fold in mouse fast-twitch skeletal muscle. Addition of LPS, IL-1β, or TNF-α directly to C2C12 myoblasts increased IL-6 protein (6- to 8-fold) and IL-6 mRNA (5- to 10-fold). The response to all three stimuli was completely blocked by the JNK inhibitor SP-600125 but not as effectively by other MAP kinase inhibitors. SP-600125 blocked LPS-stimulated IL-6 synthesis dose dependently at both the RNA and protein level. SP-600125 was as effective as the synthetic glucocorticoid dexamethasone at inhibiting IL-6 expression. SP-600125 inhibited IL-6 synthesis when added to cells up to 60 min after LPS stimulation, but its inhibitory effect waned with time. LPS stimulated IL-6 mRNA in both myoblasts and myotubes, but myoblasts showed a proportionally greater LPS-induced increase in IL-6 protein expression compared with myotubes. SP-600125 and the proteasomal inhibitor MG-132 blocked LPS-induced degradation of IκB-α/ϵ and LPS-stimulated expression of IκB-α mRNA. Yet, only SP-600125 and not MG-132 blocked LPS-induced IL-6 mRNA expression. This suggests that IL-6 gene expression is a downstream target of JNK in C2C12 myoblasts.

scholarly journals Proteins containing peptide sequences related to Lys-Phe-Glu-Arg-Gln are selectively depleted in liver and heart, but not skeletal muscle, of fasted rats

1991 ◽  
Vol 275 (1) ◽  
pp. 165-169 ◽  
Author(s):  
S S Wing ◽  
H L Chiang ◽  
A L Goldberg ◽  
J F Dice
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Time Course ◽  
Polyclonal Antibodies ◽  
Protein Loss ◽  
Cultured Fibroblasts ◽  
Cytosolic Proteins ◽  
Mammalian Tissues ◽  
Fasted Rats

In response to serum withdrawal, when overall rates of proteolysis increase in cultured fibroblasts, proteins containing peptide regions similar to Lys-Phe-Gln-Arg-Gln (KFERQ) are targeted to lysosomes for degradation, and the intracellular concentrations of these proteins decline [Chiang & Dice (1988) J. Biol. Chem. 263, 6797-6805]. To test whether such proteins are also selectively depleted in mammalian tissues in vivo, we have used affinity-purified polyclonal antibodies to KFERQ to detect proteins containing such sequences in tissues of fed and fasted rats. Immunoreactive cytosolic proteins were partially depleted from liver and heart of fasted rats, but the time course differed for these two tissues. Immunoreactive proteins in liver were lost during days 2 and 3 of fasting, whereas such proteins in heart were depleted within day 1 of fasting. In the same fasted rats, levels of immunoreactive cytosolic proteins did not change in two skeletal muscles, the dark soleus and the pale extensor digitorum longus. Immunoreactive proteins in a myofibrillar fraction were also partially depleted in heart, but not in skeletal muscles, of fasted rats. The most likely explanation for these results is that the protein loss in different tissues upon fasting results from selective activation of different proteolytic pathways. The increased proteolysis in liver and heart of fasted animals includes activation of the KFERQ-selective lysosomal pathway, whereas increased proteolysis in skeletal muscle does not.

Tissue glycogen fractions of the hypothermic rat, hamster, and turtle

1964 ◽  
Vol 207 (1) ◽  
pp. 42-46 ◽  
Author(s):  
W. S. Platner ◽  
J. L. Shields ◽  
F. A. Purdy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Utilization ◽  
Bilateral Adrenalectomy ◽  
Hepatic Glycogen ◽  
Labile Fraction ◽  
Fasted Rats

Hypothermia in fasted rats caused reduction of both glycogen fractions in liver and heart but did not affect skeletal muscle. Forced respiration during hypothermia prevented the reduction of residual glycogen in heart, but did not otherwise alter the tissue glycogen response to hypothermia. Bilateral adrenalectomy did not prevent the loss in hypothermia of either glycogen fraction from heart or liver. Prevention of shivering by curare during hypothermia failed to maintain control levels of liver or heart glycogen fractions. Incorporation of intraperitoneal glucose-C14 into tissue glycogen of hypothermic rats was increased in soluble and residual fractions of heart, but not in liver or muscle. It was concluded that disappearance of hepatic glycogen in hypothermia may be due to an accelerated glucose utilization by myocardium, and furthermore, that soluble glycogen is the more labile fraction. The same tissues of hamsters and turtles showed no changes in either glycogen fraction due to hypothermia.

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