scholarly journals Effects of membrane transport activity and cell metabolism on the unbound drug concentrations in the skeletal muscle and liver of drugs: A microdialysis study in rats

2021 ◽  
Vol 9 (5) ◽  
Author(s):  
Shuyao Wang ◽  
Chun Chen ◽  
Chi Guan ◽  
Liping Qiu ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Membrane Transport ◽  
Cell Metabolism ◽  
Transport Activity ◽  
Drug Concentrations ◽  
Microdialysis Study

Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat

2003 ◽  
Vol 285 (1) ◽  
pp. E98-E105 ◽  
Author(s):  
Erik J. Henriksen ◽  
Mary K. Teachey ◽  
Zachary C. Taylor ◽  
Stephan Jacob ◽  
Arne Ptock ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Zucker Rat ◽  
Transport Activity ◽  
Insulin Resistant ◽  
Obese Zucker Rat ◽  
Cla Isomers ◽  
Muscle Glucose Transport

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9, trans-11-CLA (c9,t11-CLA) and trans-10, cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker ( fa/ fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced ( P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides ( r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.

scholarly journals Microdialysis Study of Imipenem Distribution in Skeletal Muscle and Lung Extracellular Fluids of Noninfected Rats

2005 ◽  
Vol 49 (6) ◽  
pp. 2356-2361 ◽  
Author(s):  
Sandrine Marchand ◽  
Claire Dahyot ◽  
Isabelle Lamarche ◽  
Olivier Mimoz ◽  
William Couet
Keyword(s):  
Skeletal Muscle ◽  
Drug Administration ◽  
Jugular Vein ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Concentration Profiles ◽  
Isoflurane Anesthesia ◽  
Leg Muscle ◽  
Microdialysis Study ◽  
Awake Rats

ABSTRACT The aim of this study was to investigate the imipenem distribution in muscle and lung interstitial fluids by microdialysis in rats and to compare the free concentrations in tissue with the free concentrations in blood. Microdialysis probes were inserted into the jugular vein, hind leg muscle, and lung. Imipenem recoveries in these three media were determined in each rat by retrodialysis by drug period before drug administration. Imipenem was infused intravenously at a dose of 120 mg · kg−1 over 30 min, and microdialysis samples were collected for 150 min. The whole study was conducted with nonhydrated rats (n = 4) and hydrated rats (n = 6) while the animals were under isoflurane anesthesia. The decay of free concentrations in blood, muscle, and lung with time were monoexponential; and the concentration profiles in these three media were virtually superimposed in both groups. Accordingly, the ratios of the area under the curve (AUC) for tissue (muscle or lung) to the AUC for blood were always virtually equal to 1. Compared to values previously determined with awake rats, clearance was reduced by 2 and 1.5 in nonhydrated and hydrated rats, respectively, but the volume of distribution was unchanged. By combining microdialysis in blood and tissues, it was possible to demonstrate that free imipenem concentrations were virtually identical in blood, muscle, and lung.

Membrane transport activity and ultradian ion flux oscillations associated with cell cycle of Thraustochytrium sp.

2001 ◽  
Vol 28 (2) ◽  
pp. 87 ◽  
Author(s):  
Lana Shabala ◽  
Sergey Shabala ◽  
Tom Ross ◽  
Tom McMeekin
Keyword(s):  
Nutritional Status ◽  
Membrane Transport ◽  
Close Association ◽  
Essential Element ◽  
Ion Flux ◽  
Transport Activity ◽  
Period Range ◽  
Bathing Medium ◽  
Zoospore Release ◽  
Cross Correlation Analysis

Membrane transport activity associated with growth and nutritional status of a marine microheterotroph Thraustochytrium sp. was studied using non-invasive ion-selective slowly vibrating microelectrodes (the MIFE technique). Net fluxes of H + , Ca 2+ and Na + underwent regular changes as the cell progressed from the zoospore to sporangium stages of development. The most pronounced change was a decrease in the net H + influx, which we suggest could be associated with the changes in cytoskeletal organization required for cell cleavage and zoospore release. As cell development progressed from the zoospore stage towards maturity, non-damping endogenous ultradian oscillations (period range of several minutes) became evident. At the sporangium stage, as many as 85% of cells possessed oscillatory membrane transport activity. It is suggested that ultradian ion flux oscillations in Thraustochytrium sp. may be causally linked with cell developmental processes. Discrete Fourier transform and cross-correlation analysis revealed a close association between oscillatory patterns of H + and Na + fluxes. The possibility that these oscillations result from the rhythmical activity of a Na + /H + co-transporter located at the plasma membrane of Thraustochytrium sp. is considered. Oscillations in net Ca 2+ flux were apparently not linked to those in H+ and Na + , and are believed to be due to some other physiological processes. Periods of net H + and Na + flux oscillations were strongly dependent on the external Na + concentrations in the bathing medium. As sodium is considered to be an essential element in Thraustochytrium sp., it is suggested that the functional role of such ultradian oscillations may be their involvement in the frequency-encoding mechanism that provides developing cells with information about environment, and nutritional status in particular.

Effects of phenylarsine oxide on stimulation of glucose transport in rat skeletal muscle

1990 ◽  
Vol 258 (4) ◽  
pp. C648-C653 ◽  
Author(s):  
E. J. Henriksen ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Cytochalasin B ◽  
Contractile Activity ◽  
Transport Activity ◽  
Rat Skeletal Muscle ◽  
Phenylarsine Oxide ◽  
Muscle Glucose Transport ◽  
Glucose Analogue ◽  
Stimulation Of

The trivalent arsenical phenylarsine oxide (PAO) inhibits insulin-stimulated glucose transport in adipocytes and skeletal muscle through direct interactions with vicinal sulfhydryls. In muscle, glucose transport is also activated by contractile activity and hypoxia. It was therefore the purpose of the present study to investigate whether vicinal sulfhydryls are involved in the stimulation of glucose transport activity in the isolated rat epitrochlearis muscle by hypoxia or contractions. PAO (greater than 5 microM) caused a twofold increase in rate of transport of the nonmetabolizable glucose analogue 3-O-methylglucose (3-MG) that was completely prevented by cytochalasin B, the vicinal dithiol dimercaptopropanol, dantrolene, or 9-aminoacridine, both inhibitors of sarcoplasmic reticulum Ca2+ release, or omission of extracellular Ca2+. Although PAO treatment (greater than or equal to 20 microM) prevented approximately 80% of the increase in 3-MG transport caused by insulin, it resulted in only a approximately 50% inhibition of the stimulation of 3-MG transport by either hypoxia or contractile activity. PAO treatment (40 microM) of muscles already maximally stimulated by insulin, contractile activity, or hypoxia did not reverse the enhanced rate of 3-MG transport. These data suggest that vicinal sulfhydryls play a greater role in the activation of glucose transport by insulin than by muscle contractions or hypoxia. The finding that PAO inhibits the stimulation of glucose transport, but does not affect glucose transport after it has been stimulated, provides evidence that vicinal sulfhydryls are involved in the pathways for glucose transport activation in muscle, but not in the glucose transport mechanism itself.

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.

Reversal of enhanced muscle glucose transport after exercise: roles of insulin and glucose

1990 ◽  
Vol 259 (5) ◽  
pp. E685-E691 ◽  
Author(s):  
E. A. Gulve ◽  
G. D. Cartee ◽  
J. R. Zierath ◽  
V. M. Corpus ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Transport Process ◽  
Sugar Transport ◽  
Transport Activity ◽  
High Concentration ◽  
Exercise Induced ◽  
Muscle Glucose Transport

Exercise stimulates insulin-independent glucose transport in skeletal muscle and also increases the sensitivity of the glucose transport process in muscle to insulin. A previous study [D. A. Young, H. Wallberg-Henriksson, M. D. Sleeper, and J. O. Holloszy. Am. J. Physiol. 253 (Endocrinol. Metab. 16): E331–E335, 1987] showed that the exercise-induced increase in glucose transport activity disappears rapidly when rat epitrochlearis muscles are incubated for 3 h in vitro in the absence of insulin and that 7.5 microU/ml insulin in the incubation medium apparently slowed the loss of enhanced sugar transport. We examined whether addition of insulin several hours after exercise increases glucose transport to the same extent as continuous insulin exposure. Addition of 7.5 microU/ml insulin 2.5 h after exercise (when glucose transport has returned to basal levels) increased sugar transport to the same level as that which resulted from continuous insulin exposure. This finding provides evidence for an increase in insulin sensitivity rather than a slowing of reversal of the exercise-induced increase in insulin-independent glucose transport activity. Glucose transport was enhanced only at submaximal, not at maximal, insulin concentrations. Exposure to a high concentration of glucose and a low insulin concentration reduced the exercise-induced increase in insulin-sensitive glucose transport. Incubation with a high concentration of 2-deoxy-D-glucose (2-DG) did not alter the increase in insulin sensitivity, even though a large amount of 2-DG entered the muscle and was phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Insulin-sensitive regulation of glucose transport and GLUT4 translocation in skeletal muscle of GLUT1 transgenic mice

1998 ◽  
Vol 337 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Garret J. ETGEN ◽  
William J. ZAVADOSKI ◽  
Geoffrey D. HOLMAN ◽  
E. Michael GIBBS
Keyword(s):  
Skeletal Muscle ◽  
Cell Surface ◽  
Transgenic Mice ◽  
Glucose Transport ◽  
Hind Limb ◽  
Glucose Transporter ◽  
Glut4 Translocation ◽  
Transport Activity ◽  
Fast Twitch Muscle ◽  
Fast Twitch

Skeletal muscle glucose transport was examined in transgenic mice overexpressing the glucose transporter GLUT1 using both the isolated incubated-muscle preparation and the hind-limb perfusion technique. In the absence of insulin, 2-deoxy-d-glucose uptake was increased ∼ 3–8-fold in isolated fast-twitch muscles of GLUT1 transgenic mice compared with non-transgenic siblings. Similarly, basal glucose transport activity was increased ∼ 4–14-fold in perfused fast-twitch muscles of transgenic mice. In non-transgenic mice insulin accelerated glucose transport activity ∼ 2–3-fold in isolated muscles and to a much greater extent (∼ 7–20-fold) in perfused hind-limb preparations. The observed effect of insulin on glucose transport in transgenic muscle was similarly dependent upon the technique used for measurement, as insulin had no effect on isolated fast-twitch muscle from transgenic mice, but significantly enhanced glucose transport in perfused fast-twitch muscle from transgenic mice to ∼ 50–75% of the magnitude of the increase observed in non-transgenic mice. Cell-surface glucose transporter content was assessed via 2-N-4-(l-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(d -mannos-4-yloxy)-2-propylamine photolabelling methodology in both isolated and perfused extensor digitorum longus (EDL). Cell-surface GLUT1 was enhanced by as much as 70-fold in both isolated and perfused EDL of transgenic mice. Insulin did not alter cell-surface GLUT1 in either transgenic or non-transgenic mice. Basal levels of cell-surface GLUT4, measured in either isolated or perfused EDL, were similar in transgenic and non-transgenic mice. Interestingly, insulin enhanced cell-surface GLUT4 ∼ 2-fold in isolated EDL and ∼ 6-fold in perfused EDL of both transgenic and non-transgenic mice. In summary, these results reveal differences between isolated muscle and perfused hind-limb techniques, with the latter method showing a more robust responsiveness to insulin. Furthermore, the results demonstrate that muscle overexpressing GLUT1 has normal insulin-induced GLUT4 translocation and the ability to augment glucose-transport activity above the elevated basal rates.

Inhibitors such as staurosporine, H-7 or polymyxin B cannot be used in skeletal muscle to prove the role of protein kinase C on insulin action

1992 ◽  
Vol 12 (5) ◽  
pp. 413-424 ◽  
Author(s):  
Anna Gumà ◽  
Purificación Muñoz ◽  
Marta Camps ◽  
Xavier Testar ◽  
Manuel Palacín ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Action ◽  
Lactate Production ◽  
Polymyxin B ◽  
Transport Activity ◽  
System A ◽  
Kinase C

The precise role of protein kinase C in insulin action in skeletal muscle is not well defined. Based on the fact that inhibitors of protein kinase C block some insulin effects, it has been concluded that some of the biological actions of insulin are mediated via protein kinase C. In this study, we present evidence that inhibitors of protein kinase C such as staurosporine, H-7 or polymyxin B cannot be used to ascertain the role of protein kinase C in skeletal muscle. This is based on the following experimental evidences: a) staurosporine, H-7 and polymyxin B markedly block in muscle the effect of insulin on System A transport activity; however, this effect of insulin is not mimicked in muscle by TPA-induced stimulation of protein kinase C, b) H-7 and polymyxin B block insulin action on System A transport activity in an additive manner to the inhibitory effect of phorbol esters, c) staurosporine, H-7 and polymyxin B block the effect of insulin on lactate production, a process that is activated by insulin and TPA in an additive fashion, and d) staurosporine completely blocks the tyrosine kinase activity of insulin receptors partially purified from rat skeletal muscle.

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