Biomedical subjects

J L Ivy

Publications and source records attributed to J L Ivy.

At least 19 recordsLinked to original sources

PubMed1997

Contraction-induced intracellular signals and their relationship to muscle GLUT-4 concentration.

This investigation used a model of increased skeletal muscle contractile activity to evaluate whether the adenylate cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) pathway and/or the high-energy phosphate state of the muscle might be temporally related to the contraction-induced increase in skeletal muscle GLUT-4 protein concentration. Plantaris and gastrocnemius muscles of Sprague-Dawley rats were subjected to 3, 7, 14, or 28 days of chronic low-frequency electrical stimulation (10 Hz, 24 h/day). GLUT-4 protein concentration was slightly reduced after 3 days of electrical stimulation, similar to control values at 7 days and significantly elevated above control at 14 days (53%, P < 0.05) and 28 days (338%, P < 0.05) of stimulation. ATP, creatine phosphate, creatine, and P, were inversely related to GLUT-4 protein concentration. Adenylate cyclase activity increased with electrical stimulation and was significantly related to the increased GLUT-4 protein. cAMP was significantly increased at 14 days of stimulation and remained elevated through 28 days. These results demonstrate that both the adenylate cyclase-cAMP pathway and the high-energy phosphate state of the muscle are temporally related to elevations in skeletal muscle GLUT-4 protein concentration in response to chronic low-frequency electrical stimulation and, as such, suggest that both may comprise a component of the intracellular signal that regulates the contraction-induced increase in skeletal muscle GLUT-4 protein concentration.

Adenylyl Cyclases↗

PubMed1996

Overexpression of hexokinase II in transgenic mice. Evidence that increased phosphorylation augments muscle glucose uptake.

Hexokinase II (HKII) is the predominant isozyme expressed in peripheral insulin-responsive tissues. To explore the role of HKII in muscle glucose metabolism, two lines of transgenic mice were generated where overexpression was restricted to striated muscle; HKII protein levels and activity were increased by 3-8-fold. Oral glucose tolerance, intravenous insulin tolerance, and insulin and lactate levels were unaffected in transgenic mice. There was a trend toward increased levels of muscle glycogen; however, glucose-6-phosphate levels were increased by 43% in transgenic skeletal muscle following in vivo glucose and insulin administration. Using 2-[3H]deoxyglucose as a tracer, in vitro basal and insulin-stimulated glucose uptake were determined in extensor digitorum longus, soleus, and epitrochlearis muscles. Maximal insulin-stimulated glucose uptake was increased by 17% (extensor digitorum longus), 34% (soleus), and 90% (epitrochlearis) in transgenic muscles; basal and submaximal glucose uptake was also modestly increased in soleus and epitrochlearis. These data suggest that increased muscle HKII (corresponding to the upper end of the physiologic range) may not be sufficient to augment net in vivo glucose homeostasis. However, glucose phosphorylation can represent a rate-limiting step for skeletal muscle glucose utilization since muscle glucose-6-phosphate levels are increased during in vivo hyperinsulinemia and hyperglycemia; furthermore, basal and insulin-mediated muscle glucose uptake can be increased by a selective increase in HKII expression.

Amino Acid Sequence↗

PubMed1996

Glucose transport and GLUT4 protein distribution in skeletal muscle of GLUT4 transgenic mice.

The aim of the present investigation was to determine whether the subcellular distribution and insulin-stimulated translocation of the GLUT4 isoform of the glucose transporter are affected when GLUT4 is overexpressed in mouse skeletal muscle, and if the overexpression of GLUT4 alters maximal insulin-stimulated glucose transport and metabolism. Rates of glucose transport and metabolism were assessed by hind-limb perfusion in GLUT4 transgenic (TG) mice and non-transgenic (NTG) controls. Glucose-transport activity was determined under basal (no insulin), submaximal (0.2 m-unit/ml) and maximal (10 m-units/ml) insulin conditions using a perfusate containing 8 mM 3-O-methyl-D-glucose. Glucose metabolism was quantified by perfusing the hind limbs for 25 min with a perfusate containing 8 mM glucose and 10 m-units/ml insulin. Under basal conditions, there was no difference in muscle glucose transport between TG (1.10 +/- 0.10 mumol/h per g; mean +/- S.E.M.) and NTG (0.93 +/- 0.16 mumol/h per g) mice. However, TG mice displayed significantly greater glucose-transport activity during submaximal (4.42 +/- 0.49 compared with 2.69 +/- 0.33 mumol/h per g) and maximal (11.68 +/- 1.13 compared with 7.53 +/- 0.80 mumol/h per g) insulin stimulation. Nevertheless, overexpression of the GLUT4 protein did not alter maximal rates of glucose metabolism. Membrane purification revealed that, under basal conditions, plasma-membrane (approximately 12-fold) and intracellular-membrane (approximately 4-fold) GLUT4 protein concentrations were greater in TG than NTG mice. Submaximal insulin stimulation did not increase plasma-membrane GLUT4 protein concentration whereas maximal insulin stimulation increased this protein in both NTG (4.1-fold) and TG (2.6-fold) mice. These results suggest that the increase in insulin-stimulated glucose transport following overexpression of the GLUT4 protein is limited by factors other than the plasma-membrane GLUT4 protein concentration. Furthermore, GLUT4 overexpression is not coupled to glucose-metabolic capacity.

Animals↗

PubMed1996

Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat.

The relationship between 3-O-methyl-D-glucose transport and 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1, 3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA)-labeled cell surface GLUT-4 protein was assessed in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles of lean and obese (fa/fa) Zucker rats. In the absence of insulin, glucose transport as well as cell surface GLUT-4 protein was similar in both epitrochlearis and soleus muscles of lean and obese rats. In contrast, insulin-stimulated glucose transport rates were significantly higher for lean than obese rats in both soleus (0.74 +/- 0.05 vs. 0.40 +/- 0.02 mumol.g-1.10 min-1) and epitrochlearis (0.51 +/- 0.05 vs. 0.17 +/- 0.02 mumol.g-1.10 min-1) muscles. The ability of insulin to enhance glucose transport in fast- and slow-twitch muscles from both lean and obese rats corresponded directly with changes in cell surface GLUT-4 protein. Muscle contraction elicited similar increases in glucose transport in lean and obese rats, with the effect being more pronounced in fast-twitch (0.70 +/- 0.07 and 0.77 +/- 0.04 mumol.g-1.10 min-1 for obese and lean, respectively) than in slow-twitch muscle (0.36 +/- 0.03 and 0.40 +/- 0.02 mumol.g-1.10 min-1 for obese and lean, respectively). The contraction-induced changes in glucose transport directly corresponded with the observed changes in cell surface GLUT-4 protein. Thus the reduced glucose transport response to insulin in skeletal muscle of the obese Zucker rat appears to result directly from an inability to effectively enhance cell surface GLUT-4 protein.

Affinity Labels↗

PubMed1996

Interaction of exercise training and clenbuterol on GLUT-4 protein in muscle of obese Zucker rats.

Chronic administration of clenbuterol, a beta 2-adrenergic agonist, attenuates the exercise training-induced improvement in muscle insulin resistance of the obese Zucker rat. The present study was conducted to determine whether clenbuterol also attenuates the increase in muscle GLUT-4 protein that occurs with exercise training and whether the action of clenbuterol is related to its ability to downregulate the beta-adrenergic receptors. Female obese Zucker rats were randomly assigned to one of the following four groups: control (CON, n = 7), clenbuterol (CL, n = 8), exercise training (TR, n = 8), and clenbuterol with exercise training (CL+TR, n = 8). Rats assigned to the training groups were run on a rodent motor-driven treadmill for 6-7 wk. Rats receiving clenbuterol were intubated with 0.8 mg/kg body weight 30 min before running each day. Red quadriceps (RQ) and white quadriceps (WQ) GLUT-4 protein concentrations of TR rats were significantly greater than those of CON and CL+TR rats. The RQ GLUT-4 protein concentration of the CL+TR rats was significantly greater than that of CON rats, but this difference did not occur in the WQ. GLUT-4 protein concentrations were not different between the CON and CL rats. The patterns of RQ and WQ GLUT-4 mRNA were similar to those of their respective GLUT-4 proteins. Rats receiving daily injections of propranolol (30 mg/kg body wt), a beta-adrenergic receptor antagonist, demonstrated no increase in GLUT-4 protein in RQ or WQ after 6 wk of exercise training. These results indicate that 1) clenbuterol can attenuate the increase in muscle GLUT-4 protein associated with exercise training and 2) this effect is likely mediated by a downregulation of the beta-adrenergic receptors.

Adrenergic beta-Agonists↗

PubMed1996

Transgenic mice with muscle-specific insulin resistance develop increased adiposity, impaired glucose tolerance, and dyslipidemia.

Impaired skeletal muscle insulin receptor function is a feature of common forms of insulin resistance, including obesity and noninsulin-dependent diabetes mellitus. However, the extent to which this defect accounts for impaired muscle glucose disposal or altered in vivo glucose homeostasis remains to be established. We recently showed that transgenic mice that overexpress dominant-negative insulin receptors specifically in striated muscle have a severe defect in muscle insulin receptor-mediated signaling and modest hyperinsulinemia. Here we performed hindlimb perfusion studies to determine the impact of this defect on muscle glucose uptake and metabolism. Maximal rates of insulin-stimulated muscle 3-O-methylglucose transport were reduced by 32-40% in transgenic mice with proportional defects involving total hindlimb [14C]glucose uptake, lactate production, and muscle glycogen synthesis. To address the hypothesis that muscle insulin resistance could promote an increase in the accretion of body fat, carcass analysis was performed using two independent lines of transgenic mice. Although body weights were normal, transgenic mice had a 22-38% increase in body fat, with a reciprocal decrease (10-15%) in body protein. Mean gonadal fat pad weight was also increased in transgenic mice. Skeletal muscle histology and fiber type distribution were not affected. To determine whether muscle-specific insulin resistance was sufficient to cause impaired glucose tolerance, oral glucose tolerance tests were performed with 6-month-old transgenic and control mice. Fasting glucose levels were increased by 25%, and peak values were 22-40% higher in transgenic mice. Transgenic mice also had a 37% decrease in plasma lactate levels and modest increases in levels of plasma triglycerides and FFA (29% and 15%, respectively). We conclude that 1) severe defects in muscle insulin receptor function result in impaired insulin-stimulated glucose uptake and metabolism in this tissue; 2) muscle-specific insulin resistance can contribute to the development of obesity; and 3) a "pure" defect in insulin-mediated muscle glucose disposal is sufficient to result in impaired glucose tolerance and other features of the insulin resistance syndrome, including hyperinsulinemia and dyslipidemia.

Adipose Tissue↗

PubMed1995

Fiber type-specific effects of clenbuterol and exercise training on insulin-resistant muscle.

The interrelationships among glucose uptake, GLUT-4 protein, and citrate synthase activity in insulin-resistant skeletal muscle were investigated. Female obese (fa/fa) Zucker rats were randomly assigned to treadmill training, ingestion of the selective beta 2-adrenergic agonist clenbuterol, or sedentary control groups. After 7-8 wk of treatment, hindlimbs were perfused to determine maximal insulin-stimulated (10 mU/ml) 2-[3H]deoxy-D-glucose (2-DG) uptake. Exercise training significantly enhanced 2-DG uptake and GLUT-4 protein in red gastrocnemius and plantaris. Alternatively, 2-DG uptake was not altered in soleus after exercise training despite a 52% increase in GLUT-4 protein. The increases in GLUT-4 protein in red gastrocnemius, plantaris, and soleus of the trained rats were accompanied by increases in citrate synthase activity. In contrast to exercise training, clenbuterol administration decreased citrate synthase activity in red and white gastrocnemius, yet had no effect on GLUT-4 protein levels or maximal insulin-stimulated 2-DG uptake. Clenbuterol treatment did, however, increase citrate synthase activity and GLUT-4 protein in soleus. These findings indicate that total GLUT-4 protein largely determines the maximal rate of insulin-stimulated glucose uptake in fast-twitch muscle, whereas in slow-twitch muscle it does not. In addition, the results demonstrate that coordination of proteins governing glucose uptake and disposal may be disrupted in a fiber type-specific manner. Overall, the findings raise important questions as to whether regulation of proteins governing glucose uptake and disposal differs significantly among fiber types.

Animals↗

PubMed1994

The effects of muscle contraction and insulin on glucose-transporter translocation in rat skeletal muscle.

The effect of electrically induced muscle contraction, insulin (10 m-units/ml) and electrically-induced muscle contraction in the presence of insulin on insulin-regulatable glucose-transporter (GLUT-4) protein distribution was studied in female Sprague-Dawley rats during hindlimb perfusion. Plasma-membrane cytochalasin B binding increased approximately 2-fold, whereas GLUT-4 protein concentration increased approximately 1.5-fold above control with contractions, insulin, or insulin + contraction. Microsomal-membrane cytochalasin B binding and GLUT-4 protein concentration decreased by approx. 30% with insulin or insulin + contraction, but did not significantly decrease with contraction alone. The rate of muscle glucose uptake was assessed by determining the rate of 2-deoxy[3H]glucose accumulation in the soleus, plantaris, and red and white portions of the gastrocnemius. Both contraction and insulin increased glucose uptake significantly and to the same degree in the muscles examined. Insulin + contraction increased glucose uptake above that of insulin or contraction alone, but this effect was only statistically significant in the soleus, plantaris and white gastrocnemius. The combined effects of insulin + contraction of glucose uptake were not fully additive in any of the muscles investigated. These results suggest that (1) insulin and muscle contraction are mobilizing two separate pools of GLUT-4 protein, and (2) the increase in skeletal-muscle glucose uptake due to insulin + contraction is not due to an increase in plasma-membrane GLUT-4 protein concentration above that observed for insulin or contraction alone.

Animals↗

PubMed1994

Ventilation parallels plasma potassium during incremental and continuous variable intensity exercise.

The aim of the present investigation was to examine the relationship between plasma potassium (K+) and ventilation (VE) during incremental and prolonged continuous exercise which varied between low and moderate intensity. Seven well-trained male cyclists who had a mean maximal aerobic power (VO2max) of 69.4 +/- 2.9 ml/kg/min were recruited to participate as subjects. The graded incremental exercise bout was composed of 3 min stages set to elicit 40, 50, 60, 70, 80 and 90% VO2max. The continuous variable intensity exercise consisted of 30 min of cycling at 45% VO2max and then 6 x 16 min periods which consisted of cycling for 8 min at 75% VO2max and 8 min at 45% VO2max. During prolonged continuous exercise, VE and plasma K+ changed in a coordinated manner between the low and moderate intensity exercise bouts with the responses during the moderate intensity intervals being significantly greater (p < 0.05) than the responses during the low intensity intervals. During the incremental exercise test, a strong positive relationship between VE and plasma K+ concentration was found for each subject. However, a positive relationship and slope was also found when the VE/K+ ratio was correlated with exercise intensity (r = 0.90-0.99). This indicates that with increasing exercise intensity, the rise in VE becomes increasingly greater than the rise in plasma K+. These findings suggest that the plasma K+ concentration contributes to but may not be the sole determinant of ventilatory regulation during exercise.

Adult↗

PubMed1994

Effects of pyruvate on the metabolism and insulin resistance of obese Zucker rats.

Female obese Zucker rats aged 5 wk were randomly assigned to a control diet or one of two experimental diets. Experimental diets contained 6% of energy as pyruvate in the form of calcium-pyruvate (Ca-pyr) or 6% pyruvylglycine (pyr-gly). Diets were pair-fed according to the experimental group with the lowest food consumption. During the 3 wk of dietary treatment, Ca-pyr- and pyr-gly-fed rats gained significantly less weight, had a lower food-conversion efficiency, and maintained a higher resting oxygen consumption (mL.min-1 x kg-0.67) than control rats. Ca-pyr and pyr-gly also lowered the respiratory exchange ratio of the rats resulting in a 90% increase in their lipid oxidation and a 50% decrease in their carbohydrate oxidation. Glucose tolerance, assessed by an oral glucose load, was not different among treatments, but the insulin response of the pyr-gly-fed rats was significantly less than that of the control rats despite elevated plasma triglyceride concentrations in the pyr-gly-fed rats (control, 1.43 +/- 0.16 vs pyr-gly, 3.76 +/- 0.87 mmol/L). These results suggest that pyr-gly, like Ca-pyr, favorably alters the metabolism of obese Zucker rats. In addition, pyr-gly appeared to reduce the insulin resistance that develops spontaneously in obese rats.

Analysis of Variance↗

PubMed1994

Training adaptations of baboons to light and moderate treadmill exercise.

We evaluated training adaptations by 18 baboons (Papio cynocephalus anubis) to low and moderate quadrupedal walking exercise on a motorized treadmill. Moderate training produced 47% increases in lactate threshold, 63% increases in muscle citrate synthetase activity, increases in percentage of Type IIc muscle fibers, and reduced plasma insulin concentrations. Low training produced only reduced plasma insulin concentrations. Only results indicate that the baboon response to exercise training was similar to that of Homo sapiens, and dependent on exercise intensity.

Animals↗

PubMed1994

Glucose uptake and GLUT-4 protein distribution in skeletal muscle of the obese Zucker rat.

The rates of muscle glucose uptake of lean and obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin), in the presence of a maximally stimulating concentration of insulin (10 mU/ml), and after muscle contraction elicited by electrical stimulation of the sciatic nerve. After perfusion, plasma and microsomal membranes were isolated from selected hindlimb muscles for determination of GLUT-4 protein distribution. Under basal conditions, rates of glucose uptake were similar for lean and obese rats despite plasma membranes from lean rats containing 82% more GLUT-4 protein than obese rats. Insulin stimulation resulted in significant increases in plasma membrane GLUT-4 protein concentration in lean but not obese rats. Glucose uptake of lean rats (35.3 +/- 4.7 mumol.h-1.g-1) in the presence of insulin was approximately fourfold greater than that of obese rats (8.8 +/- 1.3 mumol.h-1.g-1), but this difference in glucose uptake could not be completely accounted for by the difference in plasma membrane GLUT-4 protein concentration. Stimulation by contraction resulted in significant increases in plasma membrane GLUT-4 protein concentration in both lean and obese rats and similar rates of glucose uptake. These results suggest that the muscle insulin resistance of the obese Zucker rat is due to 1) a reduced plasma membrane GLUT-4 protein concentration, which results in part from an impairment in the insulin-stimulated GLUT-4 protein translocation process, and 2) a defect in the insulin-stimulated activation of this protein. However, contraction-stimulated glucose uptake, GLUT-4 protein translocation, and activation are normal in the obese Zucker rat.

4-Nitrophenylphosphatase↗

PubMed1994

Dietary supplements affect the anabolic hormones after weight-training exercise.

To examine the effect of carbohydrate and/or protein supplements on the hormonal state of the body after weight-training exercise, nine experienced male weight lifters were given water (Control) or an isocaloric carbohydrate (CHO; 1.5 g/kg body wt), protein (PRO; 1.38 g/kg body wt), or carbohydrate-protein (CHO/PRO; 1.06 g carbohydrate/kg body wt and 0.41 g protein/kg) supplement immediately and 2 h after a standardized weight-training workout. Venous blood samples were drawn before and immediately after exercise and during 8 h of recovery. Exercise induced elevations in lactate, glucose, testosterone, and growth hormone. CHO and CHO/PRO stimulated higher insulin concentrations than PRO and Control. CHO/PRO led to an increase in growth hormone 6 h postexercise that was greater than PRO and Control. Supplements had no effect on insulin-like growth factor I but caused a significant decline in testosterone. The decline in testosterone, however, was not associated with a decline in luteinizing hormone, suggesting an increased clearance of testosterone after supplementation. The results suggest that nutritive supplements after weight-training exercise can produce a hormonal environment during recovery that may be favorable to muscle growth by stimulating insulin and growth hormone elevations.

Adult↗

PubMed1993

Insulin- and contraction-stimulated translocation of GTP-binding proteins and GLUT4 protein in skeletal muscle.

Low molecular weight GTP-binding proteins and GLUT4 protein were isolated in purified plasma membrane and low density microsome fractions from rat skeletal muscle. GTP-binding proteins were detected via the ability of these proteins to bind [32P]GTP subsequent to Western blotting. GLUT4 protein was detected via the anti-GLUT4 antibody F349 subsequent to Western blotting. The possible involvement of GTP-binding proteins in the regulation of GLUT4 protein movement was investigated by examining the subcellular distribution of GTP-binding proteins and GLUT4 protein under basal conditions and following stimulation by insulin or muscle contraction. Insulin stimulation caused a 111 +/- 34.8% increase in the plasma membrane content of GTP-binding proteins which was paralleled by a 74 +/- 19.1% increase in the plasma membrane content of GLUT4 protein. The insulin-stimulated increase in plasma membrane GTP-binding proteins and GLUT4 protein occurred coincident with 27 +/- 4.6 and 33 +/- 7.4% decreases, respectively, in the low density microsome content of these proteins. In addition, muscle contraction significantly increased the plasma membrane content of GTP-binding proteins (63 +/- 18.1%) and GLUT4 protein (67 +/- 22.2%). However, with muscle contraction the concentrations of GTP-binding proteins and GLUT4 protein were not altered in low density microsome fractions. The similar patterns with which the GTP-binding proteins and GLUT4 protein responded to stimulation by insulin and muscle contraction suggests a possible, but yet unidentified functional relationship between these proteins.

Animals↗

PubMed1993

Carbohydrate metabolism during exercise in hot and thermoneutral environments.

This study compared the effects of moderately intense exercise in hot and thermoneutral environments on muscle glycogen and carbohydrate utilization. Well-trained, heat acclimatized cyclists (n = 7) rode at 73.6 +/- 1.1% maximal oxygen consumption for 60 min in a thermoneutral room (23.5 +/- 0.6 degrees C, 52.7 +/- 2.9 relative humidity) or an environmental chamber (33.7 +/- 0.1 degrees C, 49.1 +/- 1.8% relative humidity). During each exercise bout, the subjects received 125 ml of water every 15 min. Muscle biopsies from the vastus lateralis were obtained prior to and following each exercise bout. Exercise in the heat significantly elevated rectal temperature and heart rate above and reduced body weight and plasma volume below that produced by exercise in a thermoneutral environment. Plasma glucose and blood lactate concentrations were similar between treatments prior to exercise, but increased to a greater concentration (p < 0.05) when exercise was performed in the heat. No differences between treatments were found for blood glycerol or free fatty acid concentrations, carbohydrate oxidation or muscle glycogen utilization. These results suggest that moderately intense exercise in the heat, as opposed to a thermoneutral environment, does not increase the rate of muscle glycogenolysis or carbohydrate oxidation in well conditioned, heat acclimatized subjects.

Acclimatization↗

PubMed1993

Effects of exercise training on skeletal muscle glucose uptake and transport.

Exercise training increases the concentration of GLUT-4 protein in skeletal muscle that is associated with an increase in maximal insulin-stimulated glucose transport. The purpose of this study was to determine whether exercise training results in a long-lasting increase in insulin-stimulated glucose transport in rat skeletal muscle. Glucose uptake and skeletal muscle 3-O-methyl-D-glucose (3-MG) transport were determined during hindlimb perfusion in the presence of a maximally stimulating concentration of insulin (10 mU/ml). Hindlimb glucose uptake was approximately 29% above sedentary (Sed) levels in rats examined within 24 h (24H) of their last exercise session. However, when rats were examined 48 h (48H) after their last exercise session, hindlimb glucose uptake was not different from Sed levels. Maximal 3-MG transport was enhanced, above Sed levels, in red (RG; 72% increase) and white (WG; 44% increase) gastrocnemius and plantaris (Plan; 67% increase) muscles, but not soleus (Sol), of 24H rats. GLUT-4 protein content was significantly elevated in those muscles that exhibited enhanced 3-MG transport in 24H rats. GLUT-4 protein content was also elevated in RG, WG, and Plan of 48H rats and was not different from 24H rats. Despite the elevated GLUT-4 protein content, 3-MG transport in 48H rats was only slightly, although statistically not significantly, higher than in Sed rats. These results provide evidence that exercise training does not result in a persistent increase in skeletal muscle glucose uptake or transport, despite an increase in GLUT-4 protein content.

3-O-Methylglucose↗

PubMed1993

Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats.

This study compared the effects of aerobic exercise training and chronic administration of the selective beta 2-adrenergic agonist clenbuterol on whole body and skeletal muscle insulin resistance in obese (fa/fa) Zucker rats. Obese rats were randomly assigned to training, clenbuterol, or sedentary control groups. Lean littermates served as a second control group. After 4-5 wk of treatment, an oral glucose tolerance test was performed, followed 1 wk later by hindlimb perfusion, during which time the rates of glucose uptake and 3-O-methyl-D-glucose (3-MG) transport were assessed in the presence of a submaximal (500 microU/ml) insulin concentration. Training resulted in a significant increase in citrate synthase and cytochrome oxidase activity in the recruited muscles. Clenbuterol induced a large increase in muscle mass but provoked a significant decrease in oxidative enzyme activity and beta-adrenergic receptor density. Both treatments increased glucose tolerance and reduced the postglucose insulin response, with the improvements being more pronounced in the clenbuterol group. However, only exercise training improved insulin-stimulated hindlimb muscle glucose uptake (11.37 +/- 0.65, 8.73 +/- 0.77, and 8.27 +/- 0.41 mumol.g-1.h-1 for trained, clenbuterol, and sedentary control groups, respectively) and 3-MG transport. These results suggest that aerobic exercise training attenuated the insulin-resistant condition in the obese Zucker rat by a mechanism other than or in addition to beta 2-adrenergic receptor activation.

3-O-Methylglucose↗

PubMed1993

Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats.

The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin-stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Nitrophenylphosphatase↗