Activation of the A1 adenosine receptor increases insulin-stimulated glucose transport in isolated rat soleus muscle

2007 ◽  
Vol 32 (4) ◽  
pp. 701-710 ◽  
Author(s):  
Farah S.L. Thong ◽  
Jamie S.V. Lally ◽  
David J. Dyck ◽  
Felicia Greer ◽  
Arend Bonen ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Soleus Muscle ◽  
Adenosine Receptor ◽  
Adenosine Diphosphate ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Endogenous Adenosine ◽  
Selective Agonist ◽  
Rat Soleus Muscle ◽  
Muscle Glucose Transport

The A1 adenosine receptor (A1AR) has been suggested to participate in insulin- and contraction-stimulated glucose transport in skeletal muscle, but the qualitative and quantitative nature of the effect are controversial. We sought to determine if A1AR is expressed in rat soleus muscle and then characterize its role in glucose transport in this muscle. A1AR mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. To examine the role of adenosine in 3-O-methylglucose transport, isolated muscles were exposed to adenosine deaminase and α,β-methylene adenosine diphosphate to remove endogenous adenosine and were left unstimulated (basal) or stimulated with insulin. To assess the functional participation of A1AR in 3-O-methylglucose transport, muscles were incubated with A1-selective agonist and (or) antagonist in the absence of endogenous adenosine and with or without insulin. A1AR mRNA was expressed in soleus muscle and A1AR was present at the plasma membrane. Removal of endogenous adenosine reduced glucose transport in response to 100 μU/mL insulin (~50%). The A1-selective agonist, N6-cyclopentyladenosine, increased submaximal (100 μU/mL) insulin-stimulated glucose transport in a dose-dependent manner (0.001–1.0 μmol/L). This stimulatory effect was inhibited by the A1-selective receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine in a concentration-dependent manner (0.001–1.0 μmol/L). However, neither activation nor inhibition of A1AR altered basal or maximal (10 mU/mL) insulin-stimulated glucose transport. Our results suggest that adenosine contributes ~50% to insulin-stimulated muscle glucose transport by activating the A1AR. This effect is limited to increasing insulin sensitivity, but not to either basal or maximal insulin-stimulated glucose uptake in rat soleus muscle.

Fibrinogen binding to the integrin αIIbβ3 modulates store-mediated calcium entry in human platelets

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2648-2656 ◽  
Author(s):  
Juan A. Rosado ◽  
Else M. Y. Meijer ◽  
Karly Hamulyak ◽  
Irena Novakova ◽  
Johan W. M. Heemskerk ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Integrin Αiibβ3 ◽  
Fibrinogen Binding

Abstract Effects of the occupation of integrin αIIbβ3 by fibrinogen on Ca++signaling in fura-2–loaded human platelets were investigated. Adding fibrinogen to washed platelet suspensions inhibited increases in cytosolic [Ca++] concentrations ([Ca++]i) evoked by adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner in the presence of external Ca++ but not in the absence of external Ca++ or in the presence of the nonselective cation channel blocker SKF96365, indicating selective inhibition of Ca++entry. Fibrinogen also inhibited store-mediated Ca++ entry (SMCE) activated after Ca++ store depletion using thapsigargin. The inhibitory effect of fibrinogen was reversed if fibrinogen binding to αIIbβ3 was blocked using RDGS or abciximab and was absent in platelets from patients homozygous for Glanzmann thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation of SMCE in platelets occurs through conformational coupling between the intracellular stores and the plasma membrane and requires remodeling of the actin cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or thapsigargin in control cells and in cells loaded with the Ca++ chelator dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase p60src to the cytoskeleton. These results indicate that the binding of fibrinogen to integrin αIIbβ3 inhibits the activation of SMCE in platelets by a mechanism that may involve modulation of the reorganization of the actin cytoskeleton and the cytoskeletal association of p60src. This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected to low-level stimuli in vivo.

Changes in [Ca2+]i induced by several glucose transport-enhancing stimuli in rat epitrochlearis muscle

2003 ◽  
Vol 94 (5) ◽  
pp. 1813-1820 ◽  
Author(s):  
Shin Terada ◽  
Isao Muraoka ◽  
Izumi Tabata
Keyword(s):  
Glucose Transport ◽  
Quantitative Information ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Fura 2 ◽  
Sprague Dawley Rats ◽  
Intracellular Ca ◽  
Resting Muscle ◽  
Krebs Henseleit Buffer

The purpose of the present investigation was to establish a method for estimating intracellular Ca2+ concentrations ([Ca2+]i) in isolated rat epitrochlearis muscles. Epitrochlearis muscles excised from 4-wk-old male Sprague-Dawley rats were loaded with a fluorescent Ca2+indicator, fura 2-AM, for 60–90 min at 35°C in oxygenated Krebs-Henseleit buffer. After fura 2 loading and subsequent 20-min incubation, the intensities of 500-nm fluorescence, induced by 340- and 380-nm excitation lights (Ftotal340 and Ftotal380), were measured. The fluorescences specific to fura-2 (Ffura 2340 and Ffura 2380) were calculated by subtracting the non-fura 2-specific component from Ftotal340 and Ftotal380, respectively. The ratio of Ffura 2340 to Ffura 2380 was calculated as R, and the change in the ratio from the baseline value (ΔR) was used as an index of the change in [Ca2+]i. In resting muscle, ΔR was stable for 60 min. Incubation for 20 min with caffeine (3–10 mM) significantly increased ΔR in a concentration-dependent manner. Incubation with hypoxic Krebs-Henseleit buffer for 10–60 min significantly elevated ΔR, depending on the duration of the incubation. Incubation with 50 μM N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide for 20 min significantly elevated ΔR ( P < 0.05). No significant increases in ΔR were observed during incubation for 20 min with 2 mM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside or with 2 mU/ml insulin. These results demonstrated that, by using the fura 2-AM fluorescence method, the changes in [Ca2+]i can be monitored in the rat epitrochlearis muscle and suggest that the method can be utilized to observe quantitative information regarding [Ca2+]i that may be involved in contraction- and hypoxia-stimulated glucose transport activity in skeletal muscle.

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries

1996 ◽  
Vol 1 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Roberto Pedrinelli
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Adenosine Receptor ◽  
Guanosine Monophosphate ◽  
Muscarinic Agonist ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adenosine Receptor Agonist ◽  
Synthase Inhibitor

Background To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. Methods and Results Specimens were mounted on a myograph and relaxed through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A2-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. Conclusion Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A2 adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3’ 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

scholarly journals Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

2015 ◽  
Vol 309 (3) ◽  
pp. R295-R303 ◽  
Author(s):  
Laelie A. Snook ◽  
Emery M. Nelson ◽  
David J. Dyck ◽  
David C. Wright ◽  
Graham P. Holloway
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Serum Insulin ◽  
Current Data ◽  
Signaling Mechanism ◽  
Akt Phosphorylation ◽  
Glucose Challenge ◽  
Muscle Glucose Transport

Several gastrointestinal proteins have been identified to have insulinotropic effects, including glucose-dependent insulinotropic polypeptide (GIP); however, the direct effects of incretins on skeletal muscle glucose transport remain largely unknown. Therefore, the purpose of the current study was to examine the role of GIP on skeletal muscle glucose transport and insulin signaling in rats. Relative to a glucose challenge, a mixed glucose+lipid oral challenge increased circulating GIP concentrations, skeletal muscle Akt phosphorylation, and improved glucose clearance by ∼35% ( P < 0.05). These responses occurred without alterations in serum insulin concentrations. In an incubated soleus muscle preparation, GIP directly stimulated glucose transport and increased GLUT4 accumulation on the plasma membrane in the absence of insulin. Moreover, the ability of GIP to stimulate glucose transport was mitigated by the addition of the PI 3-kinase (PI3K) inhibitor wortmannin, suggesting that signaling through PI3K is required for these responses. We also provide evidence that the combined stimulatory effects of GIP and insulin on soleus muscle glucose transport are additive. However, the specific GIP receptor antagonist (Pro3)GIP did not attenuate GIP-stimulated glucose transport, suggesting that GIP is not signaling through its classical receptor. Together, the current data provide evidence that GIP regulates skeletal muscle glucose transport; however, the exact signaling mechanism(s) remain unknown.

scholarly journals Furosemide decreases the sensitivity of glucose transport to insulin in skeletal muscle in vitro

1998 ◽  
Vol 139 (1) ◽  
pp. 118-122 ◽  
Author(s):  
G Dimitriadis ◽  
B Leighton ◽  
M Parry-Billings ◽  
C Tountas ◽  
S Raptis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Transport Process ◽  
Glucose Utilization ◽  
Glucose Disposal ◽  
Rat Soleus Muscle ◽  
Lactate Formation

The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.

scholarly journals Anandamide inhibits transport-related oxygen consumption in the loop of Henle by activating CB1 receptors

2013 ◽  
Vol 304 (4) ◽  
pp. F376-F381 ◽  
Author(s):  
Guillermo B. Silva ◽  
Douglas K. Atchison ◽  
Luis I. Juncos ◽  
Néstor H. García
Keyword(s):  
Oxygen Consumption ◽  
Receptor Antagonist ◽  
Cannabinoid Receptors ◽  
Cb1 Receptors ◽  
Dependent Manner ◽  
Cb2 Receptor ◽  
Na Transport ◽  
Concentration Dependent Manner ◽  
Selective Agonist

The energy required for active Na chloride reabsorption in the thick ascending limb (TAL) depends on oxygen consumption and oxidative phosphorylation (OXP). In other cells, Na transport is inhibited by the endogenous cannabinoid anandamide through the activation of the cannabinoid receptors (CB) type 1 and 2. However, it is unclear whether anandamide alters TAL transport and the mechanisms that could be involved. We hypothesized that anandamide inhibits TAL transport via activation of CB1 receptors and NO. For this, we measured oxygen consumption (QO2) in TAL suspensions to monitor the anandamide effects on transport and OXP. Anandamide reduced QO2 in a concentration-dependent manner. During Na-K-2Cl cotransport and Na/H exchange inhibition, anandamide did not inhibit TAL QO2. To test the role of the cannabinoid receptors, we used specific agonists and antagonists of CB1 and CB2 receptors. The CB1-selective agonist WIN55212–2 reduced QO2 in a concentration-dependent manner. Also, the CB1 receptor antagonist rimonabant blocked the effect of anandamide on QO2. In contrast, the CB2-selective agonist JHW-133 had no effect on QO2, while the CB2 receptor antagonist AM-630 failed to block the anandamide effects on QO2. To confirm these results, we measured CB1 and CB2 receptor expression and only CB1 expression was detected. Because CB1 receptors are strong nitric oxide synthase (NOS) stimulators and NO inhibits transport in TALs, we evaluated the role of NO. Anandamide stimulated NO production and the NOS inhibitor NG-nitro-l-arginine methyl ester blocked the anandamide effects on QO2. We conclude that anandamide inhibits TAL Na transport-related QO2 via activation of CB1 receptor and NOS.

Effect of hypothermia on 2-deoxy-glucose transport, insulin binding and insulin sensitivity of the rat soleus muscle

1997 ◽  
Vol 4 (3) ◽  
pp. 205-212
Author(s):  
Teresa Torlińska ◽  
Józef Langfort ◽  
Paweł Maćkowiak ◽  
Tomasz Hryniewiecki ◽  
Hanna Kaciuba-Uściłko ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Insulin Binding ◽  
Rat Soleus Muscle

Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle

1987 ◽  
Vol 252 (4) ◽  
pp. E492-E499 ◽  
Author(s):  
T. Clausen ◽  
J. A. Flatman
Keyword(s):  
Glucose Transport ◽  
Soleus Muscle ◽  
Sugar Transport ◽  
Resting Membrane Potential ◽  
Exchange System ◽  
Glucose Transport System ◽  
Rat Soleus Muscle ◽  
Possible Cause ◽  
K Transport ◽  
Stimulation Of

To identify possible cause-effect relationships between changes in active Na+-K+ transport, resting membrane potential, and glucose transport, the effects of insulin and epinephrine were compared in rat soleus muscle. Epinephrine, which produced twice as large a hyperpolarization as insulin, induced only a modest increase in sugar transport. Ouabain, at a concentration (10(-3) M) sufficient to block active Na+-K+ transport and the hyperpolarization induced by the two hormones, did not interfere with sugar transport stimulation. After Na+ loading in K+-free buffer, the return to K+-containing standard buffer caused marked stimulation of active Na+-K+ transport, twice the hyperpolarization produced by insulin but no change in sugar transport. The insulin-induced activation of the Na+-K+ pump leads to decreased intracellular Na+ concentration and hyperpolarization, but none of these events can account for the concomitant activation of the glucose transport system. The stimulating effect of insulin on active Na+-K+ transport was not suppressed by amiloride, indicating that in intact skeletal muscle it is not elicited by a primary increase in Na+ influx via the Na+/H+-exchange system.

Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model

2003 ◽  
Vol 284 (6) ◽  
pp. L1012-L1019 ◽  
Author(s):  
Ming Fan ◽  
Weixi Qin ◽  
S. Jamal Mustafa
Keyword(s):  
Mouse Model ◽  
Adenosine Receptor ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Transcript Levels ◽  
Allergen Sensitization ◽  
Selective Agonist ◽  
Dose Dependent ◽  
Allergic Mouse

We recently reported that adenosine caused bronchoconstriction and enhanced airway inflammation in an allergic mouse model. In this study, we further report the characterization of the subtype of adenosine receptor(s) involved in bronchoconstriction. 5′-( N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine agonist, elicited bronchoconstriction in a dose-dependent manner. Little effects of N 6-cyclopentyladenosine (A1-selective agonist) and 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine (A2A-selective agonist) compared with NECA were observed in this model. 2-Chloro- N 6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-β-d-ribofuranosyl]adenosine, an A3-selective receptor agonist, produced a dose-dependent bronchoconstrictor response, which was blocked by selective A3 antagonist 2,3-diethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate (MRS1523). However, MRS1523 only partially inhibited NECA-induced bronchoconstriction. Neither selective A1 nor A2A antagonists affected NECA-induced bronchoconstriction. Enprofylline, a relatively selective A2B receptor antagonist, blocked partly NECA-induced bronchoconstriction. Furthermore, a combination of enprofylline and MRS1523 completely abolished NECA-induced bronchoconstrictor response. Using RT-PCR, we found that all four adenosine receptor subtypes are expressed in control lungs. Allergen sensitization and challenge significantly increased transcript levels of the A2B and A3receptors, whereas the A1 receptor message decreased. No change in transcript levels of A2A receptors was observed after allergen sensitization and challenge. These findings suggest that A2B and A3 adenosine receptors play an important role in adenosine-induced bronchoconstriction in our allergic mouse model. Finally, whether the airway effects of the receptor agonists/antagonists are direct or indirect needs further investigations.

Mechanism of insulin-induced activation of Na(+)-K(+)-ATPase in isolated rat soleus muscle

1991 ◽  
Vol 261 (2) ◽  
pp. C224-C230 ◽  
Author(s):  
E. Weil ◽  
S. Sasson ◽  
Y. Gutman
Keyword(s):  
Soleus Muscle ◽  
Time Course ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Insulin Stimulation ◽  
K Uptake ◽  
Sequence Of Events ◽  
Rat Soleus Muscle ◽  
Isolated Rat ◽  
Stimulation Of

Insulin augments Na(+)-K(+)-ATPase activity in skeletal muscles. It has been proposed that the sequence of events is activation of Na(+)-H+ antiporter, increased intracellular Na+ concentration ( [Na+]i), and stimulation of Na(+)-K+ pump. We have used isolated rat soleus muscles to test this hypothesis. Insulin increased the ouabain-suppressible K+ uptake in a dose- and time-dependent manner. The maximal effect was observed at 50-100 mU/ml insulin. Stimulation of K+ uptake was accompanied by increased specific [3H]ouabain binding and lowered [Na+]i. The ionophore monensin, which promotes Na(+)-H+ exchange, also increased the rate of ouabain-suppressible K+ uptake in soleus muscle, with a maximal effect obtained at 10-100 microM ionophore. However, this increase was accompanied by an elevation of [Na+]i. In the presence of 10-100 microM monensin, addition of 100 mU/ml insulin further increased K+ uptake but reduced [Na+]i. The effect on K+ uptake was additive. Ouabain (10(-3) M) completely suppressed the effect of insulin on [Na+]i. Insulin had no effect on the magnitude or the time course of insulin stimulation of K+ uptake. Thus equal stimulation of Na(+)-K(+)-ATPase by insulin was observed when [Na+]i was elevated (under monensin) or lowered (under amiloride). These data suggest that activation of Na(+)-K(+)-ATPase in soleus muscle by insulin is not secondary to stimulation of Na(+)-H+ antiporter.

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