scholarly journals Epinephrine inhibits insulin-stimulated muscle glucose transport

2002 ◽  
Vol 93 (5) ◽  
pp. 1638-1643 ◽  
Author(s):  
Desmond G. Hunt ◽  
John L. Ivy
Keyword(s):  
Glucose Transport ◽  
Pi3 Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase Activation ◽  
Essential Step ◽  
Muscle Types ◽  
Slow Twitch ◽  
Muscle Glucose Transport ◽  
Fast Twitch ◽  
Epinephrine Concentration

We recently demonstrated that epinephrine could inhibit the activation by insulin of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase) in skeletal muscle (Hunt DG, Zhenping D, and Ivy JL. J Appl Physiol 92: 1285–1292, 2002). Activation of PI3-kinase is recognized as an essential step in the activation of muscle glucose transport by insulin. We therefore investigated the effect of epinephrine on insulin-stimulated glucose transport in both fast-twitch (epitrochlearis) and slow-twitch (soleus) muscle of the rat by using an isolated muscle preparation. Glucose transport was significantly increased in the epitrochlearis and soleus when incubated in 50 and 100 μU/ml insulin, respectively. Activation of glucose transport by 50 μU/ml insulin was inhibited by 24 nM epinephrine in both muscle types. This inhibition of glucose transport by epinephrine was accompanied by suppression of IRS-1-associated PI3-kinase activation. However, when muscles were incubated in 100 μU/ml insulin, 24 nM epinephrine was unable to inhibit IRS-1-associated PI3-kinase activation or glucose transport. Even when epinephrine concentration was increased to 500 nM, no attenuating effect was observed on glucose transport. Results of this study indicate that epinephrine is capable of inhibiting glucose transport activated by a moderate, but not a high, physiological insulin concentration. The inhibition of glucose transport by epinephrine appears to involve the inhibition of IRS-1-associated PI3-kinase activation.

Clenbuterol prevents epinephrine from antagonizing insulin-stimulated muscle glucose uptake

2002 ◽  
Vol 92 (3) ◽  
pp. 1285-1292 ◽  
Author(s):  
Desmond G. Hunt ◽  
Zhenping Ding ◽  
John L. Ivy
Keyword(s):  
Glucose Uptake ◽  
Kinase Activity ◽  
Pi3 Kinase ◽  
Intracellular Concentration ◽  
Insulin Receptor Substrate ◽  
Phosphatidylinositol 3 Kinase ◽  
Rat Skeletal Muscle ◽  
Slow Twitch ◽  
Chronic Clenbuterol ◽  
Fast Twitch

In the present study, we investigated the effects of chronic clenbuterol treatment on insulin-stimulated glucose uptake in the presence of epinephrine in isolated rat skeletal muscle. Insulin (50 μU/ml) increased glucose uptake in both fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles. In the presence of 24 nM epinephrine, insulin-stimulated glucose uptake was completely suppressed. This suppression of glucose uptake by epinephrine was accompanied by an increase in the intracellular concentration of glucose 6-phosphate and a decrease in insulin-receptor substrate-1-associated phosphatidylinositol 3-kinase (IRS-1/PI3-kinase) activity. Clenbuterol treatment had no direct effect on insulin-stimulated glucose uptake. However, after clenbuterol treatment, epinephrine was ineffective in attenuating insulin-stimulated muscle glucose uptake. This ineffectiveness of epinephrine to suppress insulin-stimulated glucose uptake occurred in conjunction with its inability to increase the intracellular concentration of glucose 6-phosphate and attenuate IRS-1/PI3-kinase activity. Results of this study indicate that the effectiveness of epinephrine to inhibit insulin-stimulated glucose uptake is severely diminished in muscle from rats pretreated with clenbuterol.

Skeletal muscle glucose transport in obese Zucker rats after exercise training

1989 ◽  
Vol 66 (6) ◽  
pp. 2635-2641 ◽  
Author(s):  
J. L. Ivy ◽  
J. T. Brozinick ◽  
C. E. Torgan ◽  
G. M. Kastello
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
Transport Process ◽  
Fiber Type ◽  
Zucker Rat ◽  
Muscle Insulin Resistance ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Muscle Glucose Transport ◽  
Fast Twitch

Exercise training has been found to reduce the muscle insulin resistance of the obese Zucker rat (fa/fa). The purpose of the present study was to determine whether this reduction in muscle insulin resistance was associated with an improvement in the glucose transport process and if it was fiber-type specific. Rats were randomly assigned to a sedentary or training group. Training consisted of treadmill running at 18 m/min up an 8% grade, 1.5 h/day, 5 days/wk, for 6–8 wk. The rate of muscle glucose transport was assessed in the absence of insulin and in the presence of a physiological (0.15 mU/ml), a submaximal (1.50 mU/ml), and a maximal (15.0 mU/ml) insulin concentration by determining the rate of 3-O-methyl-D-glucose (3-OMG) accumulation during hindlimb perfusion. The average 3-OMG transport rate of the red gastrocnemii (fast-twitch oxidative-glycolytic fibers) was significantly higher in the trained compared with the sedentary obese rats in the absence of insulin and in the presence of the three insulin concentrations. Significant improvements in 3-OMG transport were also observed in the plantarii (mixed fibers) of trained obese rats in the presence of 0, 0.15, and 15.0 mU/ml insulin. Training appeared to have little effect on the insulin-stimulated 3-OMG transport of the soleus (slow-twitch oxidative fibers) or white gastrocnemius (fast-twitch glycolytic fibers). The results suggest that the improvement in the muscle insulin resistance of the obese Zucker rat after moderate endurance training was associated with an improvement in the glucose transport process but that it was fiber-type specific.

Perfused rat hindlimb is suitable for skeletal muscle glucose transport measurements

1998 ◽  
Vol 274 (1) ◽  
pp. E184-E191 ◽  
Author(s):  
Jørgen F. P. Wojtaszewski ◽  
Allan B. Jakobsen ◽  
Thorkil Ploug ◽  
Erik A. Richter
Keyword(s):  
Electrical Stimulation ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Insulin Stimulation ◽  
Transport Measurements ◽  
Perfusate Flow ◽  
Muscle Glucose Transport ◽  
Fast Twitch

It has been postulated that the perfused rat hindlimb is unsuitable for measurements of muscle glucose transport [P. Hansen, E. Gulve, J. Gao, J. Schluter, M. Mueckler, and J. Holloszy. Am. J. Physiol. 268 ( Cell Physiol. 37): C30–C35, 1995]. The aim of the present study was therefore to critically evaluate the suitability of this preparation for glucose transport measurements using the extracellular marker mannitol and the glucose analogs 3- O-methyl-d-glucose or 2-deoxy-d-glucose. In all three muscle fiber types studied, the rate of 2-deoxy-d-glucose uptake during perfusion was linear from 1 to 40 min during maximal insulin stimulation and from 1 to 15 min during maximal electrical stimulation. Uptake of 2-deoxy-d-glucose was not increased by an increase in perfusate flow. Combined stimulation with a maximal insulin concentration and electrical stimulation elicited additive effects on 2-deoxy-d-glucose uptake in slow- and fast-twitch oxidative but not in fast-twitch glycolytic muscle fibers. Furthermore, in muscles having high glucose transport capacities 3- O-methyl-d-glucose is less suitable than 2-deoxy-d-glucose because of rapidly developing nonlinearity of accumulation. Our findings clearly demonstrate that the perfused hindlimb is suitable for measurements of muscle glucose transport and that the most feasible glucose analog for this purpose is 2-deoxy-d-glucose.

scholarly journals Phosphatidylinositol 3-kinase activity is important for progesterone-induced Xenopus oocyte maturation.

1993 ◽  
Vol 13 (11) ◽  
pp. 6661-6666 ◽  
Author(s):  
A J Muslin ◽  
A Klippel ◽  
L T Williams
Keyword(s):  
Oocyte Maturation ◽  
Kinase Activity ◽  
Sh2 Domain ◽  
Pi3 Kinase ◽  
Meiotic Maturation ◽  
Xenopus Laevis Oocytes ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase Activation ◽  
Phosphatidylinositol 3

In somatic cells, phosphatidylinositol 3-kinase (PI3 kinase) is a critical intermediary in growth factor-induced mitogenesis. We have examined the role of this enzyme in meiotic maturation of Xenopus laevis oocytes. PI3 kinase activity was present in immunoprecipitates of the p85 subunit of PI3 kinase from immature oocytes and markedly increased following progesterone stimulation. Injection of bacterially expressed protein corresponding to the C-terminal SH2 domain of p85 (SH2-C) inhibited progesterone-induced PI3 kinase activation and meiotic maturation. Injection of protein corresponding to the N-terminal SH2 domain or the SH3 domain of p85 did not inhibit PI3 kinase activation or maturation. SH2-C did not inhibit oocyte maturation induced by c-mos RNA injection. In addition, radiolabelled SH2-C was used to probe oocyte lysates, revealing that a novel 200-kDa protein bound to SH2-C. This protein may be an important mediator of progesterone-induced lipid metabolism in oocytes.

Prolactin induced tyrosine phosphorylation of p59fyn may mediate phosphatidylinositol 3-kinase activation in Nb2 cells

1997 ◽  
Vol 19 (3) ◽  
pp. 347-350 ◽  
Author(s):  
KA al-Sakkaf ◽  
PR Dobson ◽  
BL Brown
Keyword(s):  
Tyrosine Phosphorylation ◽  
Pi3 Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Src Tyrosine Kinase ◽  
Kinase Activation ◽  
Nb2 Cells ◽  
Co Precipitation ◽  
Dose Dependent ◽  
Phosphatidylinositol 3

Our previous studies indicated that PI3-kinase is involved in prolactin (PRL) signalling. We have now examined the involvement of the src tyrosine kinase, fyn, in PRL-induced the activation of PI3-kinase in the rat lymphoma cell line, Nb2. Cells were stimulated with increasing doses of PRL, lysed and immunoprecipitated with anti-fyn specific antibody. Then PI3-kinase activity was measured as the increase in the phosphorylation of phosphatidylinositol to phosphatidylinositol 3-phosphate separated by TLC. Our data indicated that, in PRL treated cells, co-precipitation of PI3-kinase with anti-fyn antiserum led to time and dose-dependent activation of PI3-kinase in vitro and that this activation was blocked by the addition of LY294002. However, LY294002 appeared to have no effect on fyn autophosphorylation. Furthermore, the physical association of PI3-kinase with fyn was confirmed by Western blot analysis employing the same specific antisera. These data provide evidence that PRL-induced activation of PI3-kinase may be mediated by the tyrosine phosphorylation of fyn in Nb2 cells.

scholarly journals Thyroid receptor plasticity in striated muscle types: effects of altered thyroid state

1998 ◽  
Vol 274 (6) ◽  
pp. E1018-E1026 ◽  
Author(s):  
Fadia Haddad ◽  
Anqi X. Qin ◽  
Samuel A. McCue ◽  
Kenneth M. Baldwin
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Type I ◽  
Thyroid State ◽  
Muscle Types ◽  
Slow Twitch ◽  
Thyroid Receptor ◽  
Altered Thyroid ◽  
Fast Twitch ◽  
Skeletal Muscle Types

This study examined nuclear thyroid receptor (TR) maximum binding capacity (Bmax), dissociation constant ( K d), and TR isoform (α1, α2, β1) mRNA expression in rodent cardiac, “fast-twitch white,” “fast-twitch red,” and “slow-twitch red” muscle types as a function of thyroid state. These analyses were performed in the context of slow-twitch type I myosin heavy-chain (MHC) expression, a 3,5,3′-triiodothyronine (T3)-regulated gene that displays varying responsiveness to T3 in the above tissues. Nuclear T3 binding analyses show that the skeletal muscle types express more TRs per unit DNA than cardiac muscle, whereas the latter has a lower K d than the former. Altered thyroid state had little effect on either cardiac Bmax or K d, whereas hypothyroidism increased Bmax in the skeletal muscle types without affecting its K d. Cardiac muscle demonstrated the greatest mRNA signal of TR-β1 compared with the other muscle types, whereas the TR-α1mRNA signals were more abundant in the skeletal muscle types, especially fast-twitch red. Hyperthyroidism increased the ratio of β1 to α1 and decreased the ratio of α2- to α1+β1-mRNA signal across the muscle types, whereas hypothyroidism caused the opposite effects. The nuclear T3affinity correlated significantly with the TR-β1 mRNA expression but not with TR-α1 mRNA expression. Collectively, these findings suggest that, despite a divergent pattern of TR mRNA expression in the different muscle types, these patterns follow similar qualitative changes under altered thyroid state. Furthermore, TR expression pattern cannot account for the quantitative and qualitative changes in type I MHC expression that occur in the different muscle types.

scholarly journals Mechanisms for increased insulin-stimulated Akt phosphorylation and glucose uptake in fast- and slow-twitch skeletal muscles of calorie-restricted rats

2011 ◽  
Vol 300 (6) ◽  
pp. E966-E978 ◽  
Author(s):  
Naveen Sharma ◽  
Edward B. Arias ◽  
Abhijit D. Bhat ◽  
Donel A. Sequea ◽  
Steve Ho ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Dose ◽  
Heat Shock Protein 90 ◽  
Regulatory Proteins ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Pi3k Activity ◽  
Phosphatase 2A ◽  
Slow Twitch ◽  
Fast Twitch

Calorie restriction [CR; ∼65% of ad libitum (AL) intake] improves insulin-stimulated glucose uptake (GU) and Akt phosphorylation in skeletal muscle. We aimed to elucidate the effects of CR on 1) processes that regulate Akt phosphorylation [insulin receptor (IR) tyrosine phosphorylation, IR substrate 1-phosphatidylinositol 3-kinase (IRS-PI3K) activity, and Akt binding to regulatory proteins (heat shock protein 90, Appl1, protein phosphatase 2A)]; 2) Akt substrate of 160-kDa (AS160) phosphorylation on key phosphorylation sites; and 3) atypical PKC (aPKC) activity. Isolated epitrochlearis (fast-twitch) and soleus (slow-twitch) muscles from AL or CR (6 mo duration) 9-mo-old male F344BN rats were incubated with 0, 1.2, or 30 nM insulin and 2-deoxy-[3H]glucose. Some CR effects were independent of insulin dose or muscle type: CR caused activation of Akt (Thr308and Ser473) and GU in both muscles at both insulin doses without CR effects on IRS1-PI3K, Akt-PP2A, or Akt-Appl1. Several muscle- and insulin dose-specific CR effects were revealed. Akt-HSP90 binding was increased in the epitrochlearis; AS160 phosphorylation (Ser588and Thr642) was greater for CR epitrochlearis at 1.2 nM insulin; and IR phosphorylation and aPKC activity were greater for CR in both muscles with 30 nM insulin. On the basis of these data, our working hypothesis for improved insulin-stimulated GU with CR is as follows: 1) elevated Akt phosphorylation is fundamental, regardless of muscle or insulin dose; 2) altered Akt binding to regulatory proteins (HSP90 and unidentified Akt partners) is involved in the effects of CR on Akt phosphorylation; 3) Akt effects on GU depend on muscle- and insulin dose-specific elevation in phosphorylation of Akt substrates, including, but not limited to, AS160; and 4) greater IR phosphorylation and aPKC activity may contribute at higher insulin doses.

scholarly journals Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice.

1996 ◽  
Vol 16 (6) ◽  
pp. 3074-3084 ◽  
Author(s):  
T Yamauchi ◽  
K Tobe ◽  
H Tamemoto ◽  
K Ueki ◽  
Y Kaburagi ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Map Kinase ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Pi3 Kinase ◽  
Insulin Receptor Substrate ◽  
Wild Type ◽  
Insulin Receptor Substrate 1 ◽  
Kinase Activation ◽  
Deficient Mice

We and others recently generated mice with a targeted disruption of the insulin receptor substrate 1 (IRS-1) gene and demonstrated that they exhibited growth retardation and had resistance to the glucose-lowering effect of insulin. Insulin initiates its biological effects by activating at least two major signalling pathways, one involving phosphatidylinositol 3-kinase (PI3-kinase) and the other involving a ras/mitogen-activated protein kinase (MAP kinase) cascade. In this study, we investigated the roles of IRS-1 and IRS-2 in the biological action in the physiological target organs of insulin by comparing the effects of insulin in wild-type and IRS-1-deficient mice. In muscles from IRS-1-deficient mice, the responses to insulin-induced PI3-kinase activation, glucose transport, p70 S6 kinase and MAP kinase activation, mRNA translation, and protein synthesis were significantly impaired compared with those in wild-type mice. Insulin-induced protein synthesis was both wortmannin sensitive and insensitive in wild-type and IRS-1 deficient mice. However, in another target organ, the liver, the responses to insulin-induced PI3-kinase and MAP kinase activation were not significantly reduced. The amount of tyrosine-phosphorylated IRS-2 (in IRS-1-deficient mice) was roughly equal to that of IRS-1 (in wild-type mice) in the liver, whereas it only 20 to 30% of that of IRS-1 in the muscles. In conclusion, (i) IRS-1 plays central roles in two major biological actions of insulin in muscles, glucose transport and protein synthesis; (ii) the insulin resistance of IRS-1-deficient mice is mainly due to resistance in the muscles; and (iii) the degree of compensation for IRS-1 deficiency appears to be correlated with the amount of tyrosine-phosphorylated IRS-2 (in IRS-1-deficient mice) relative to that of IRS-1 (in wild-type mice).

scholarly journals Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle

Diabetes ◽  
2000 ◽  
Vol 49 (8) ◽  
pp. 1281-1287 ◽  
Author(s):  
W. Derave ◽  
H. Ai ◽  
J. Ihlemann ◽  
L. A. Witters ◽  
S. Kristiansen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Transport ◽  
Kinase Activation ◽  
Protein Kinase Activation ◽  
Slow Twitch Muscle ◽  
Slow Twitch ◽  
Amp Activated Protein Kinase
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