Exercise Training and Muscle Insulin Resistance

Two treatments that increase skeletal muscle insulin action are exercise training and high-carbohydrate diet. The purpose of the present study was to determine whether exercise training and a diet high in carbohydrates could function synergistically to reduce the muscle insulin resistance in the obese Zucker rat. Obese rats 4 wk of age were randomly assigned to an exercise or sedentary group. Each group was subdivided by diet with one-half of the rats fed a high-carbohydrate diet and one-half fed a high-fat diet. Lean Zucker rats fed the high-fat diet were used as controls. Muscle insulin resistance was assessed during hindlimb perfusion with a submaximally stimulating concentration of insulin. Exercise training and the high-carbohydrate diet increased the rate of muscle glucose uptake in the obese rat by 46 and 53%, respectively. More importantly, the combined effect of exercise training and high-carbohydrate diet was greater than the sum of their individual effects. Glycogen synthesis paralleled glucose uptake and was the major pathway for intracellular glucose disposal. Muscle glucose uptake for exercise-trained, high-carbohydrate fed obese rats was comparable with that of lean controls. It is concluded that exercise training and the high-carbohydrate diet functioned synergistically to reduce the muscle insulin resistance in the obese rat.

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Skeletal Muscle Insulin Resistance: Roles of Fatty Acid Metabolism and Exercise

Physical Therapy ◽

10.2522/ptj.20080018 ◽

2008 ◽

Vol 88 (11) ◽

pp. 1279-1296 ◽

Cited By ~ 87

Author(s):

Lorraine P Turcotte ◽

Jonathan S Fisher

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acid ◽

Exercise Training ◽

Aerobic Exercise ◽

Glucose Uptake ◽

Muscle Cells ◽

Aerobic Exercise Training ◽

Muscle Insulin Resistance ◽

Skeletal Muscle Insulin Resistance

The purpose of this review is to provide information about the role of exercise in the prevention of skeletal muscle insulin resistance, that is, the inability of insulin to properly cause glucose uptake into skeletal muscle. Insulin resistance is associated with high levels of stored lipids in skeletal muscle cells. Aerobic exercise training decreases the amounts of these lipid products and increases the lipid oxidative capacity of muscle cells. Thus, aerobic exercise training may prevent insulin resistance by correcting a mismatch between fatty acid uptake and fatty acid oxidation in skeletal muscle. Additionally, a single session of aerobic exercise increases glucose uptake by muscle during exercise, increases the ability of insulin to promote glucose uptake, and increases glycogen accumulation after exercise, all of which are important to blood glucose control. There also is some indication that resistance exercise may be effective in preventing insulin resistance. The information provided is intended to help clinicians understand and explain the roles of exercise in reducing insulin resistance.

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Interaction of aerobic exercise training and clenbuterol: effects on insulin-resistant muscle

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.4.1471 ◽

1993 ◽

Vol 75 (4) ◽

pp. 1471-1476 ◽

Cited By ~ 23

Author(s):

C. E. Torgan ◽

G. J. Etgen ◽

J. T. Brozinick ◽

R. E. Wilcox ◽

J. L. Ivy

Keyword(s):

Insulin Resistance ◽

Exercise Training ◽

Aerobic Exercise ◽

Glucose Uptake ◽

Adrenergic Receptor ◽

Citrate Synthase ◽

Aerobic Exercise Training ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Muscle Insulin Resistance

The effects of aerobic exercise training, chronic administration of the selective beta 2-adrenergic agonist clenbuterol, and the combination of these two treatments on muscle insulin resistance were compared in female obese (fa/fa) Zucker rats. Rats were randomly assigned to trained, clenbuterol, clenbuterol-trained, or control groups. Training consisted of treadmill running for 2 h/day at 18 m/min up an 8% grade. Clenbuterol was administered by intubation (0.4–0.8 mg.kg body wt-1 x day-1) approximately 30 min before the rats ran each day. After 8 wk of treatment, muscle insulin resistance was assessed via hindlimb perfusion in the presence of 8 mM glucose and a submaximal (500 microU/ml) insulin concentration. Training increased citrate synthase activity (mumol.g wet wt-1 x min-1) by 32–74% and insulin-stimulated glucose uptake by 45%. Clenbuterol ingestion induced a 17–29% increase in muscle mass but decreased citrate synthase activity by 34–42% and had no effect on muscle glucose uptake. Administration of clenbuterol to rats that exercise trained prevented the training-induced improvement in insulin-stimulated glucose uptake and attenuated the increases in citrate synthase activity. In addition, both clenbuterol-treated groups displayed a 42% decrease in beta-adrenergic receptor density. The results indicate that clenbuterol administration, possibly through beta-adrenergic receptor downregulation, attenuated a cellular reaction essential for the exercise training-induced increase in citrate synthase activity and improvement in skeletal muscle insulin resistance of the obese Zucker rat.

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Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5′-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside

Journal of Endocrinology ◽

10.1677/joe-09-0202 ◽

2009 ◽

Vol 202 (3) ◽

pp. 441-451 ◽

Cited By ~ 41

Author(s):

Donato A Rivas ◽

Ben B Yaspelkis ◽

John A Hawley ◽

Sarah J Lessard

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Protein Kinase ◽

Exercise Training ◽

Ampk Activation ◽

Rat Skeletal Muscle ◽

Muscle Insulin Resistance ◽

Skeletal Muscle Insulin Resistance

The serine/threonine protein kinase, mammalian target of rapamycin (mTOR) is regulated by insulin and nutrient availability and has been proposed to play a central role as a nutrient sensor in skeletal muscle. mTOR associates with its binding partners, raptor and rictor, to form two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) respectively. We have investigated the assembly of mTORC1/2 and the activation of their downstream substrates (i.e. Akt, S6K1) in response to known effectors of mTOR, excess lipid availability and AMP-activated protein kinase (AMPK) activation/exercise training in rat skeletal muscle. The in vivo formation of mTORC1 and 2 and the activation of their respective downstream substrates were increased in response to chronic (8 weeks) consumption of a high-fat diet. Diet-induced mTORC activation and skeletal muscle insulin resistance were reversed by 4 weeks of exercise training, which was associated with enhanced muscle AMPK activation. In order to determine whether AMPK activation reverses lipid-induced mTOR activation, L6 myotubes were exposed to 0.4 mM palmitate to activate mTORC1/2 in the absence or presence of 5′-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR). Palmitate exposure (4 h) increased insulin-stimulated S6K1 Thr389 phosphorylation by 60%, indicating activation of mTORC1. AMPK activation with 1 mM AICAR abolished lipid-induced mTOR activation in vitro. Our data implicates reductions in mTOR complex activation with the reversal of lipid-induced skeletal muscle insulin resistance in response to exercise training or AICAR and identifies mTOR as a potential target for the treatment of insulin resistance.

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Muscle glucose uptake of obese Zucker rats trained at two different intensities

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.1.36 ◽

1991 ◽

Vol 70 (1) ◽

pp. 36-42 ◽

Cited By ~ 9

Author(s):

M. E. Willems ◽

J. T. Brozinick ◽

C. E. Torgan ◽

M. Y. Cortez ◽

J. L. Ivy

Keyword(s):

Insulin Resistance ◽

Exercise Training ◽

Glucose Uptake ◽

Exercise Bout ◽

Zucker Rats ◽

Muscle Insulin Resistance ◽

Obese Zucker Rat ◽

Training Response ◽

Obese Zucker Rats ◽

The Difference

Exercise training reduces the muscle insulin resistance of the obese Zucker rat. The purpose of the present study was to determine whether the magnitude of this training response is exercise intensity specific. Obese Zucker rats were randomly divided into sedentary (SED), low-intensity (LI), and high-intensity (HI) exercise groups. For the LI rats, exercise training consisted of running on a rodent treadmill at 18 m/min up an 8% grade for 90 min. Rats in the HI group ran at 24 m/min up an 8% grade for four 17-min bouts with 3 min between bouts. Both exercise groups performed the same amount of work and trained 5 days/wk for 7 wk. To evaluate muscle insulin resistance, rat hindlimbs were perfused for 30 min with perfusate containing 6 mM glucose (0.15 mu Ci of D-[14C(U)] glucose/ml) and either a maximal (10.0 mU/ml) or a submaximal (0.50 mU/ml) insulin concentration. Perfusions were performed 48–56 h after the last exercise bout and a 12-h fast. In the presence of 0.5 mU/ml insulin, the rate of muscle glucose uptake was found to be significantly faster for the HI (9.56 +/- 0.66 mumol.h-1.g-1) than for the LI (7.72 +/- 0.65 mumol.h-1.g-1) and SED (6.64 +/- 0.44 mumol.h-1.g-1) rats. The difference in glucose uptake between the LI and SED rats was not significant. In the presence of 10.0 mU/ml insulin, the rate of glucose uptake was significantly faster for the HI (16.43 +/- 1.02 mumol.h-1.g-1) than for the LI rats (13.76 +/- 0.84 mumol.h-1.g-1) and significantly faster for the LI than for the SED rats (11.02 +/- 0.35 mumol.h-1.g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

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