Beta-adrenergic modulation of insulin binding in skeletal muscle

1986 ◽  
Vol 250 (2) ◽  
pp. E198-E204
Author(s):  
B. Webster ◽  
S. R. Vigna ◽  
T. Paquette ◽  
D. J. Koerker
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Protein Phosphatase ◽  
Adrenergic Receptors ◽  
Plasma Membranes ◽  
Acute Exercise ◽  
Insulin Binding ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Adrenergic Antagonist

Both a high physiological concentration (13.1 nM) of epinephrine (E) and acute exercise (AEx) have previously been shown to increase 125I-insulin binding in skeletal muscle. To investigate the site and mechanism of the effect of epinephrine on binding and the possible link between epinephrine- and AEx-enhanced insulin binding, we measured insulin binding in three different preparations: 1) crude membranes derived from whole soleus muscle incubated in vitro with 13.1 nM E, 2) crude membranes with E present in the binding assay, and 3) purified plasma membranes with E present. Epinephrine enhanced binding in all three preparations by 169, 144, and 164%, respectively, at low concentrations of insulin but had little effect at high concentrations. Epinephrine, therefore appears to have its effect at the plasma membrane. Propranolol (10 microM), a beta-adrenergic antagonist, blocked E-enhanced insulin binding and when added to crude membranes made from soleus and extensor digitorum longus muscle of AEx rats reversed the increase in binding seen with exercise. This indicates that E-enhanced insulin binding is mediated by beta-adrenergic receptors and that AEx enhances insulin binding via beta-adrenergic receptors. Sodium orthovanadate (3 mM), a phosphotyrosyl-protein phosphatase inhibitor, also inhibited the increase in insulin binding due to E, implying that E may increase insulin binding by activating a phosphotyrosyl-protein phosphatase which decreases the phosphorylation of a plasma membrane protein, presumably the insulin receptor.

Desensitization of beta-adrenergic receptors in adipocytes causes increased insulin sensitivity of glucose transport

1996 ◽  
Vol 271 (2) ◽  
pp. E271-E276 ◽  
Author(s):  
A. Green ◽  
R. M. Carroll ◽  
S. B. Dobias
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Adrenergic Receptors ◽  
Plasma Membranes ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
High Dose ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Adipocyte Plasma Membranes

To determine the effect of desensitization of adipocyte beta-adrenergic receptors on insulin sensitivity, rats were continuously infused with isoproterenol (50 or 100 micrograms.kg-1.h-1) for 3 days by osmotic minipumps. Epididymal adipocytes were isolated. The cells from treated animals were desensitized to isoproterenol, as determined by response of lipolysis (glycerol release). Binding of [125I]iodocyanopindolol was decreased by approximately 80% in adipocyte plasma membranes isolated from treated rats, indicating that beta-adrenergic receptors were downregulated. Cellular concentrations of Gn alpha and Gi alpha were not altered. Insulin sensitivity was determined by measuring the effect of insulin on glucose transport (2-deoxy-[3H]glucose uptake). Cells from the isoproterenol-infused rats were markedly more sensitive to insulin than those from control rats. This was evidenced by an approximately 50% increase in maximal glucose transport rate in cells from the high-dose isoproterenol-treated rats and by an approximately 40% decrease in the half-maximal effective concentration of insulin in both groups. 125I-labeled insulin binding to adipocytes was not altered by the isoproterenol infusions, indicating that desensitization of beta-adrenergic receptors results in tighter coupling between insulin receptors and stimulation of glucose transport.

Skeletal muscle beta-adrenergic receptors: variations due to fiber type and training

1984 ◽  
Vol 246 (2) ◽  
pp. E160-E167 ◽  
Author(s):  
R. S. Williams ◽  
M. G. Caron ◽  
K. Daniel
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptors ◽  
Fiber Type ◽  
Succinic Dehydrogenase ◽  
Oxidative Capacity ◽  
Treadmill Running ◽  
Beta Adrenergic Receptors ◽  
Control Groups ◽  
Beta Adrenergic ◽  
Physiological Importance

To determine the relationship between oxidative capacity and characteristics of beta-adrenergic receptors (beta AR) in skeletal muscle, selected biochemical variables were quantitated in particulate preparations from soleus and gastrocnemius muscle from rats subjected to 10 wk of treadmill running and from three control groups: free-fed, sedentary controls; food-restricted, pair-weighted controls; and animals trained by swimming. Beta AR density and isoproterenol-stimulated adenylate cyclase activity were considerably greater in the slow-twitch oxidative soleus muscle than in the mixed fiber type gastrocnemius in animals from each group (P less than 0.005). Succinic dehydrogenase (SDH) activity of gastrocnemius was increased 23-42% (P less than 0.05) in runners over each of the control groups, concommitantly with a 15-27% increase (P less than 0.05) in beta AR density (Bmax for binding of 125I-cyanopindolol). In 24 animals from all four treatment groups, there was a significant correlation between SDH activity and beta AR density (r = 0.68; P less than 0.001). We conclude that BAR density correlates positively with oxidative capacity in skeletal muscle, but further studies are required to determine the physiological importance of these differences.

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles

1996 ◽  
Vol 80 (2) ◽  
pp. 699-705 ◽  
Author(s):  
T. Tsakiridis ◽  
P. P. Wong ◽  
Z. Liu ◽  
C. D. Rodgers ◽  
M. Vranic ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Skeletal Muscles ◽  
Plasma Membranes ◽  
Acute Exercise ◽  
Treadmill Running ◽  
Type I ◽  
Mrna Levels ◽  
Subunit Mrna ◽  
White Type

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.

scholarly journals Autoradiographic visualization of beta-adrenergic receptors in normal and denervated skeletal muscle.

1979 ◽  
Vol 27 (10) ◽  
pp. 1308-1311 ◽  
Author(s):  
B Lavenstein ◽  
W K Engel ◽  
N B Reddy ◽  
S Carroll
Keyword(s):  
Skeletal Muscle ◽  
Blood Vessels ◽  
Adrenergic Receptors ◽  
Cellular Localization ◽  
Muscle Fibers ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Adrenergic Blocker

Autoradiographic localization of beta-adrenergic receptors in rat skeletal muscle in vivo was achieved utilizing [125I]-iodohydroxybenzylpindolol, a potent beta-adrenergic blocker with high affinity and specificity for those receptors. In normal muscle the beta-adrenergic receptors were localized mainly to blood vessels, arterioles greater than venules, with much less concentration of grains over the fascicles of muscle fibers. One week after denervation there was an increase in binding both to blood vessels and muscle fibers, more so in soleus and gactrocnemius than in extensor digitorum longus. While these results parallel in vitro biochemical studies, they dictate caution when inferring cellular localization of beta-adrenergic receptors (and other molecules) solely on the basis of biochemical techniques applied to subcellular fractions of whole-organ homogenates.

Potentiation of surfactant release in fetal lung by thyroid hormone action

1984 ◽  
Vol 56 (6) ◽  
pp. 1621-1626 ◽  
Author(s):  
D. K. Das ◽  
J. Ayromlooi ◽  
D. Bandyopadhyay ◽  
S. Bandyopadhyay ◽  
A. Neogi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Adrenergic Receptors ◽  
Actinomycin D ◽  
Binding Capacity ◽  
Fetal Lung ◽  
Lavage Fluid ◽  
Beta Adrenergic Receptors ◽  
Lung Maturation ◽  
Beta Adrenergic ◽  
Adrenergic Antagonist

Thyroid hormone has been shown to accelerate fetal lung development, but the mechanisms by which this hormone acts are yet unknown. Since this hormone may act indirectly by potentiating the action of endogenous catecholamines, we studied this mechanism by measuring beta-adrenergic receptors in fetal lung. Fetal rabbits at 27 days of gestation were treated with triiodothyronine (T3), 100 micrograms/100 g, in the presence and absence of propranolol, 200 micrograms/100 g, or actinomycin D, 20 micrograms/100 g. Fetuses were killed by decapitation either after 4 or 24 h of T3 treatment. The beta-adrenergic antagonist l-[3H]dihydroalprenolol was used to directly estimate the number and affinity of beta-adrenergic receptor in lung membranes. T3 increased the number of beta-adrenergic receptors in fetal lung, but the affinity of binding did not change. The enhancement of binding capacity after 4 h of T3 treatment was not inhibited by actinomycin D. However, 24-h T3-mediated stimulation was partially blocked by actinomycin D. In addition, T3 stimulated the catecholamine content, adenylate cyclase activity, and adenosine 3′,5′-cyclic monophosphate content of lung. T3 increased the lecithin-to-sphingomyelin ratio, phosphatidylglycerol, and disaturated phosphatidylcholine content of the pulmonary lavage fluid. These parameters were completely inhibited by propranolol after 4 h and partially inhibited by actinomycin D after 24 h. Thus thyroid hormone enhances lung maturation by increasing the number of beta-adrenergic receptors in fetal lung.

scholarly journals Localization of β-adrenergic receptors in A431 cells in situ. Effect of chronic exposure to agonist

1989 ◽  
Vol 263 (2) ◽  
pp. 533-538 ◽  
Author(s):  
H Y Wang ◽  
M Berrios ◽  
C C Malbon
Keyword(s):  
Adrenergic Receptors ◽  
High Speed ◽  
Radioligand Binding ◽  
Specific Binding ◽  
Polyacrylamide Gel Electrophoresis ◽  
Beta Adrenergic Receptors ◽  
A431 Cells ◽  
Beta Adrenergic ◽  
Adrenergic Antagonist

The status of beta-adrenergic receptors was investigated in A431 cells exposed to chronic stimulation by the beta-adrenergic agonist, (-)-isoproterenol. Specific binding of beta-adrenergic antagonist (-)-[125I]iodocyanopindolol declined to 60-80% below control values within 12 h of agonist treatment. This decline in ligand binding was also observed in high-speed membrane fractions prepared from agonist-treated cells. Immunoblots probed with anti-receptor antibodies revealed both that beta-adrenergic receptors from untreated and treated cells migrated as 65,000-Mr peptides and that the cellular complement of receptor was unchanged. Indirect immunofluorescence localization of beta-adrenergic receptors was comparable in control (untreated) cells and cells challenged with (-)-isoproterenol for 1, 12, or 24 h. Thus receptor complement, migration on SDS/polyacrylamide-gel electrophoresis, and localization in situ are largely unaffected by agonist stimulation. Receptor binding of antagonist radioligands, in contrast, is markedly down-regulated in cells stimulated chronically with beta-adrenergic agonists. These data argue in favour of agonist-induced alteration(s) in the conformation of the receptor that preclude radioligand binding rather than agonist-induced receptor sequestration and/or degradation.

scholarly journals Occupancy of G alpha s-linked receptors uncouples chemoattractant receptors from their stimulus-transduction mechanisms in the neutrophil

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 1052-1057
Author(s):  
BN Cronstein ◽  
KA Haines ◽  
S Kolasinski ◽  
J Reibman
Keyword(s):  
Protein Kinase ◽  
Adrenergic Receptors ◽  
Plasma Membranes ◽  
Kinase Inhibitor ◽  
Neutrophil Function ◽  
Gtpase Activity ◽  
Dibutyryl Camp ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Transduction Mechanisms

Adenosine and adrenergic agonists modulate neutrophil function by ligating their specific receptors (adenosine A2 and beta-adrenergic) on the neutrophil. When occupied, adenosine A2 and beta-adrenergic receptors stimulate, presumably via G alpha s, an increase in intracellular 3′, 5′ cyclic adenosine monophosphate (cAMP). cAMP affects cellular functions, in part, via protein kinase-mediated phosphorylation. Therefore, we determined whether inhibition of protein kinase A activity by KT5720 (10 mumol/L) reversed the inhibition of FMLP-stimulated O2- generation by 5′N-ethylcarboxamidoadenosine (NECA), the most potent adenosine A2 agonist, and by isoproterenol a potent beta-adrenergic agonist. KT5720 did not affect O2- generation stimulated by FMLP (125% +/- 13% of control, n = 5). However, KT5720 completely reversed inhibition of O2- generation by dibutyryl cAMP (DbcAMP, 1 mmol/L, from 26% +/- 5% to 84% +/- 25% of control, n = 5, P less than .004), but not by NECA (1 mumol/L, 26% +/- 5% v 33% +/- 7% of control, n = 5) or isoproterenol (10 mumol/L, 20% +/- 8% to 38% +/- 6% of control, n = 5). Nearly identical results were obtained using the less specific protein kinase inhibitor H-7. To determine whether occupancy of adenosine A2 or beta-adrenergic receptors inhibits neutrophil (PMN) activation by uncoupling chemoattractant receptors from G proteins, we determined the effect of NECA and isoproterenol on guanosine triphosphatase (GTPase) activity, a parameter that reflects G protein “activation,” of plasma membranes derived from human PMNs. Control GTPase activity was 138.9 pmol/mg protein/min; NECA (1 nmol/L to 1 mumol/L) and isoproterenol (10 nmol/L to 10 mumol/L) alone did not significantly affect GTPase activity. FMLP (0.1 mumol/L) increased GTPase activity by 31.9 +/- .9 pmol/mg/min, an increment that was markedly inhibited to approximately 50% of control by NECA (IC50 = 3 nmol/L, P less than .001, n = 5) and isoproterenol (IC50 = 30 nmol/L, P less than .001, n = 5). Neither cAMP nor dibutyryl cAMP (10 mumol/L and 1 mmol/L) affected resting or stimulated GTPase activity. In addition, neither adenosine nor DbcAMP affected protein phosphorylation in resting or stimulated neutrophils. Our studies are consistent with the hypothesis that ligation of G alpha s-linked receptors uncouples chemoattractant receptors from their signal-transduction mechanisms rather than inhibiting neutrophil function via cAMP-mediated effects.

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