Exercise increases susceptibility of muscle glucose transport to activation by various stimuli

1990 ◽  
Vol 258 (2) ◽  
pp. E390-E393 ◽  
Author(s):  
G. D. Cartee ◽  
J. O. Holloszy
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Sugar Transport ◽  
Insulin Binding ◽  
Insulin Mimetic ◽  
Increased Sensitivity ◽  
Muscle Glucose Transport ◽  
Glucose Analogue ◽  
Stimulation Of

The insulin sensitivity of glucose transport in skeletal muscle is enhanced after exercise. In this study, stimulation of transport of the nonmetabolizable glucose analogue 3-O-methylglucose by the insulin-mimetic agents vanadate and H2O2 was markedly enhanced in rat epitrochlearis muscles 18 h after a bout of swimming. This increase in susceptibility of the glucose transport process in muscle to stimulation by insulin-mimetic agents that act beyond the insulin-binding step provides evidence that the increased insulin sensitivity results from an effect of exercise on a later step in the activation of glucose transport. Hypoxia and insulin appear to stimulate glucose transport by different pathways in muscle as evidenced by an additivity of their maximal effects. The effect of a submaximal hypoxic stimulus on muscle sugar transport was greatly amplified 3 h after exercise. This increase in susceptibility of glucose transport to stimulation by hypoxia after exercise suggests that the increased sensitivity is not limited to the insulin sensitive pathway. In contrast to exercise (i.e., swimming), in vitro muscle contractions did not result in an increase in sensitivity of muscle glucose transport to insulin, raising the possibility that a humoral factor is necessary for this effect.

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)

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.

Contraction-induced increase in muscle insulin sensitivity: requirement for a serum factor

1994 ◽  
Vol 266 (2) ◽  
pp. E186-E192 ◽  
Author(s):  
J. Gao ◽  
E. A. Gulve ◽  
J. O. Holloszy
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Contractile Activity ◽  
Serum Factor ◽  
Enhance Insulin Sensitivity ◽  
Krebs Henseleit Buffer ◽  
Stimulation Of

The insulin sensitivity of glucose transport is enhanced in skeletal muscle after a bout of exercise. In a previous study, stimulation of washed muscles to contract in vitro, in contrast to exercise, did not result in an increase in insulin sensitivity. The purpose of the present study was to explain this apparent discrepancy. We found that, although rat epitrochlearis muscles stimulated to contract in vitro after 15 min of incubation in Krebs-Henseleit buffer did not develop increased insulin sensitivity, muscles stimulated to contract immediately after being dissected showed a small but significant enhancement of the stimulation of 3-O-methyl-D-glucose transport by 30 microU/ml insulin. Furthermore, muscles stimulated to contract in situ and then allowed to recover in vitro showed as large an increase in insulin sensitivity as that which occurs after a bout of swimming. To follow up these findings suggesting involvement of a humoral factor, we incubated epitrochlearis muscles in serum before and during contractile activity in vitro. Epitrochlearis muscle insulin sensitivity was enhanced to as great an extent after in vitro contractile activity in serum as after swimming. Experiments involving charcoal treatment, ultrafiltration, or trypsin digestion provided evidence that the serum factor that interacts with contractions to enhance insulin sensitivity is a protein.

Insulin sensitivity in adipocytes from subjects with varying degrees of glucose tolerance

1986 ◽  
Vol 251 (3) ◽  
pp. E306-E310
Author(s):  
J. E. Foley ◽  
P. Thuillez ◽  
S. Lillioja ◽  
J. Zawadzki ◽  
C. Bogardus
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Binding ◽  
Normal Glucose Tolerance ◽  
Dependent Diabetes Mellitus ◽  
Oral Glucose ◽  
Pima Indians ◽  
Wide Range

Previous studies showed that the sensitivity of glucose transport to insulin is lower in adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus and impaired glucose tolerance compared with subjects with normal glucose tolerance. This study analyzed the relationship between insulin sensitivity of glucose transport and glycemia in a large group of nondiabetic-nonglucose-intolerant subjects with a wide range of glycemic response to oral glucose. Seventy-four Pima Indians with 2-h postglucose load glucoses between 77 and 197 mg/100 ml, fasting plasma glucoses between 76 and 108 mg/100 ml, and no postload glucoses less than 199 mg/100 ml were studied. Isolated adipocytes were prepared in vitro after an abdominal fat biopsy, ED50 of insulin for glucose transport was correlated with 2-h postload glucoses, but not between insulin binding per cell or per cell surface area or in ED50 of insulin for antilipolysis and 2-h postglucose load glucoses. Although only 17% of the variation in glucose tolerance could be explained by a change in the sensitivity of glucose transport to insulin, the data suggests that a postinsulin-binding defect in the coupling of insulin binding to glucose transport may be an early step in the development of insulin resistance in human adipocytes.

Effects of wheat germ agglutinin on insulin binding and insulin sensitivity of fat cells

1980 ◽  
Vol 238 (3) ◽  
pp. E267-E275
Author(s):  
J. N. Livingston ◽  
B. J. Purvis
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Transport System ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Insulin Binding ◽  
Fat Cells ◽  
Glucose Transport System ◽  
Stimulation Of

The plant lectin (wheat germ agglutinin, WGA) produces several alterations in the ability of fat cells to bind and respond to insulin. Although WGA markedly stimulated glucose oxidation, it caused only a modest stimulation of glucose transport. WGA (0.25-20 micrograms/ml) increased the binding of insulin by adipocytes, apparently by increasing the binding affinity of the insulin receptor. With low WGA concentrations (0.25-2.5 micrograms/ml), the elevation in binding was accompanied by an increase in the sensitivity of the adipocytes to insulin stimulation of glucose transport. However, the sensitivity of these cells to vitamin K5 and H2O2 was not altered. With higher WGA concentrations (5-20 micrograms/ml), stimulation of the glucose transport system by insulin, vitamin K5, or H2O2 was markedly inhibited, an effect that is reversed by the addition of ovomucoid. These findings suggest that low WGA concentrations increase the affinity of the insulin receptor and the insulin sensitivity of the cells. At higher concentrations, the lectin appears to act at another site(s) to inhibit the activation of the transport system by insulin or other agents.

Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin

2002 ◽  
Vol 282 (1) ◽  
pp. E18-E23 ◽  
Author(s):  
Jonathan S. Fisher ◽  
Jiaping Gao ◽  
Dong-Ho Han ◽  
John O. Holloszy ◽  
Lorraine A. Nolte
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Transport ◽  
Fold Increase ◽  
Amp Kinase ◽  
Major Purpose ◽  
Acute Increase ◽  
Exercise Induced ◽  
Muscle Glucose Transport ◽  
Pkb Phosphorylation

Evidence has accumulated that activation of AMP kinase (AMPK) mediates the acute increase in glucose transport induced by exercise. As the exercise-induced, insulin-independent increase in glucose transport wears off, it is followed by an increase in muscle insulin sensitivity. The major purpose of this study was to determine whether hypoxia and 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), which also activate AMPK and stimulate glucose transport, also induce an increase in insulin sensitivity. We found that the increase in glucose transport in response to 30 μU/ml insulin was about twofold greater in rat epitrochlearis muscles that had been made hypoxic or treated with AICAR 3.5 h previously than in untreated control muscles. This increase in insulin sensitivity was similar to that induced by a 2-h bout of swimming or 10 min of in vitro electrically stimulated contractions. Neither phosphatidylinositol 3-kinase activity nor protein kinase B (PKB) phosphorylation in response to 30 μU/ml insulin was enhanced by prior exercise or AICAR treatment that increased insulin sensitivity of glucose transport. Inhibition of protein synthesis by inclusion of cycloheximide in the incubation medium for 3.5 h after exercise did not prevent the increase in insulin sensitivity. Contractions, hypoxia, and treatment with AICAR all caused a two- to three-fold increase in AMPK activity over the resting level. These results provide evidence that the increase in insulin sensitivity of muscle glucose transport that follows exercise is mediated by activation of AMPK and involves a step beyond PKB in the pathway by which insulin stimulates glucose transport.

Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro

2000 ◽  
Vol 88 (3) ◽  
pp. 1072-1075 ◽  
Author(s):  
Edward O. Ojuka ◽  
Lorraine A. Nolte ◽  
John O. Holloszy
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Strong Evidence ◽  
Culture Medium ◽  
Glut 4 ◽  
Muscle Glucose Transport ◽  
Stimulation Of

Exercise acutely stimulates muscle glucose transport and also brings about an adaptive increase in the capacity of muscle for glucose uptake by inducing increases in GLUT-4 and hexokinase.1 Recent studies have provided evidence that activation of AMP protein kinase (AMPK) is involved in the stimulation of glucose transport by exercise. The purpose of this study was to determine whether activation of AMPK is also involved in mediating the adaptive increases in GLUT-4 and hexokinase. To this end, we examined the effect of incubating rat epitrochlearis muscles in culture medium for 18 h in the presence or absence of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which enters cells and is converted to the AMP analog ZMP, thus activating AMPK. Exposure of muscles to 0.5 mM AICAR in vitro for 18 h resulted in an ∼50% increase in GLUT-4 protein and an ∼80% increase in hexokinase. This finding provides strong evidence in support of the hypothesis that the activation of AMPK that occurs in muscle during exercise is involved in mediating the adaptive increases in GLUT-4 and hexokinase.

Effect of soleus unweighting on stimulation of insulin-independent glucose transport activity

1993 ◽  
Vol 74 (4) ◽  
pp. 1653-1657 ◽  
Author(s):  
E. J. Henriksen ◽  
L. S. Ritter
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Insulin Binding ◽  
Transport Activity ◽  
Transporter Protein ◽  
Protein Levels ◽  
Independent Mechanism ◽  
Male Wistar Rats ◽  
Stimulation Of

Unweighting of the rat soleus by tail-cast suspension results in increased insulin action on stimulation of glucose transport, which can be explained, at least in part, by increased insulin binding and enhanced glucose transporter protein levels. Glucose transport is also activated by an insulin-independent mechanism stimulated by in vitro muscle contractions or hypoxia. Therefore, the purpose of this study was to determine if soleus unweighting leads to an enhanced response of the insulin-independent pathway for stimulation of glucose transport. The hindlimbs of juvenile male Wistar rats were suspended by a tail-cast system for 3 or 6 days. Glucose transport activity in isolated soleus strips (approximately 18 mg) was then assessed by using 2-deoxy-[1,2–3H]glucose (2-DG) uptake. Insulin (2 mU/ml) had a progressively enhanced effect on 2-DG uptake after 3 and 6 days of unweighting (+44 and +72% vs. control, respectively; both P < 0.001). At these same times, there was no difference between groups for activation of 2-DG uptake by maximally effective treatments with contractions (10 tetanuses), hypoxia (60 min), or caffeine (5 mM). These results indicate that the enhanced capacity for stimulation of glucose transport after soleus unweighting is restricted to the insulin pathway, with no apparent enhancement of the insulin-independent pathway.

Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM

1987 ◽  
Vol 253 (3) ◽  
pp. E300-E304 ◽  
Author(s):  
H. Yki-Jarvinen ◽  
K. Kubo ◽  
J. Zawadzki ◽  
S. Lillioja ◽  
A. Young ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
American Indians ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Binding ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Insulin Dependent ◽  
Obese Subjects

It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. We compared the sensitivities of glucose transport and antilipolysis to insulin and measured insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic (% fat, 41 +/- 1), 25 obese diabetic (% fat, 40 +/- 1), and 15 nonobese (% fat, 30 +/- 1) female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport and antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED50 for stimulation of glucose transport was higher in the obese patients with NIDDM (171 +/- 38 vs. 92 +/- 10 pM, P less than 0.005). In contrast, the ED50s for antilipolysis were similar in obese diabetic patients (32 +/- 6 pM) and obese nondiabetic subjects (27 +/- 3 pM). No difference was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder.

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.

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