An important determinant of insulin sensitivity in humans, the insulin-induced glucose uptake in skeletal muscle (directed into glycogen synthesis), has been found to be markedly enhanced in endurance-trained individuals compared with sedentary controls. This enhanced insulin action is accompanied by a decreased insulin response during an oral glucose load. Available evidence indicates that the enhanced insulin action is not a genuine training effect, but merely a lasting effect of the previous exercise session(s). In the young, insulin sensitivity increases with a single exercise session, but the increase may appear only after several training sessions in middle-aged or older individuals. The effect disappears after 3–6 days. The exercise-induced reduction in muscle glycogen is an important factor underlying the increased insulin sensitivity in the period after exercise. There are reports that endurance and strength training enhances whole-body insulin sensitivity to a similar extent, and available evidence suggests that, provided total energy expenditure is held constant, low-intensity and high-intensity exercise are equally effective in promoting insulin sensitivity. Differences in sex steroids may explain the observation of a markedly higher insulin sensitivity in women than in men. Adaptations, which might underlie the increased insulin sensitivity in trained individuals, include increases in levels of the glucose transporter protein GLUT-4 and in muscle glycogen synthase activity, a decrease in the serum triglyceride concentration and, possibly, an increase in the muscle capillary network.
ReavenGM: Role of insulin resistance in human diseaseDiabetes1988, 37:1595–1607.
2.
HortonES: Role and management of exercise in diabetes mellitusDiabetes Care1988, 11:201–211.
3.
KoivistoVAYki-JärvinenHDeFronzoRA: Physical training and insulin sensitivityDiabetes/Metabolism Reviews1988, 1:445–481.
4.
FeskensEJMLoeberJGKromhoutD: Diet and physical activity as determinants of hyperinsulinemia: The Zutphen Elderly StudyAm J Epidemiol1994, 140:350–360.
5.
Franssila-KallunkiASchalin-JänttiCGroopL: Effect of gender on insulin resistance associated with agingAm J Physiol1992, 263:E780–E785. Twentywomen and 20 men varying in age from 21 to 80 years were studied using the euglycaemic insulin clamp technique in combination with indirect calorimetry and infusion of tritium-labelled glucose. It was found that non-oxidative glucose metabolism was inversely correlated with age in the men only.
6.
NuutilaPKnuutiMJMäkiMLaineHRuotsalainenUTeräsM: Gender and insulin sensitivity in the heart and in skeletal muscles. Studies using positron emission tomographyDiabetes1995, 44:31–36. Theinsulin sensitivity of glucose uptake directed into muscle was compared in seven women and nine men (healthy and equally fit, aged 29–31 years) using [18F]-fluoro-2-deoxy-D-glucose and positron emission tomography under hyperinsulinaemic, normoglycaemic conditions. Whole-body insulin sensitivity and the rate of glucose uptake by femoral muscles were 41 and 47% greater, respectively, in the women than in the men.
7.
BogardusCLilliojaSStoneKMottD: Correlation between muscle glycogen synthetase activity and in vivo insulin action in manJ Clin Invest1984, 73:1185–1190. Insulin-mediated glucose disposal was measured in 25 individuals with varying glucose tolerances using the hyperinsulinaemic euglycaemic clamp technique at plasma insulin concentrations of 130 and 1700 μU/ml with simultaneous indirect calorimetry to assess glucose oxidation and storage rates. It was found that muscle glycogen synthase activity at the end of the euglycaemic clamp test correlated well with insulin-mediated glucose storage rates at both low and high insulin concentrations.
8.
ShulmanGRothmanDJueTSteinPDeFronzoRShulmanR.Quantitation of muscle glycogen synthesis in normal subjects and in subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopyN Engl J Med1990, 322:223–228. Therate-limiting step in muscle glycogen synthesis was measured using 13C-nuclear magnetic resonance spectroscopy (NMR) during a euglycaemic, hyperinsulinaemic clamp. The study demonstrates that during these conditions virtually all non-oxidative glucose disposal, measured using indirect calorimetry, consists of muscle glycogen synthesis.
9.
BarrettEJLiuZ: Hepatic glucose metabolism and insulin resistance in NIDDM and obesity In Baillière's Clinical Endocrinology and Metabolism. Insulin Resistance and Disease. Edited by FerranniniE.London: Baillière Tindall; 1993:875–901.
10.
Yki-JärvinenHYoungAALamkinCFoleyJE: Kinetics of glucose disposal in whole body and across the forearm in manJ Clin Invest1987, 79:1713–1719. Usingthe in-vivo kinetic approach over a wide range of glucose concentrations, this paper indicates that glucose transport is rate-limiting at physiological but not at superphysiological rates of glucose disposal.
11.
MitrakouAKelleyDVenemanTJenssenTPangburnTReillyJ: Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDMDiabetes1990, 39:1381–1390.
12.
RossettiLHuM: Skeletal muscle glycogenosis is more sensitive to insulin than is glucose transport/phosphorylation. Relation to the insulin-mediated inhibition of hepatic glucose productionJ Clin Invest1993, 92:2963–2974.
13.
Beck-NielsenHVaagADamsboPHandbergANielsenOHHenriksenJE: Insulin resistance in skeletal muscles in patients with NIDDMDiabetes Care1992, 15:418–429. Thisis a review that focuses mainly on insulin signalling during normal and insulin-resistant states. The authors conclude that the insulin resistance in NIDDM is caused by an inherited defect in the ability of insulin to activate the enzyme glycogen synthase.
14.
KlipAPaquetMR: Glucose transport and glucose transporters in muscle and their metabolic regulationDiabetes Care1990, 13:228–243.
15.
Wallberg-HenrikssonH: Glucose transport into skeletal muscle: Influence of contractile activity, insulin, catecholamines and diabetes mellitusActa Physiol Scand1987, 131 (suppl 564):1–80. Adoctoral thesis which summarizes the basal mechanisms of glucose transport into skeletal muscle and how this is influenced by contractile activity, insulin, catecholamines and diabetes mellitus.
16.
Wallberg-HenrikssonHConstableSHYoungDAHolloszyJO: Glucose transport into rat skeletal muscle: Interaction between exercise and insulinJ Appl Physiol1988, 65:909–913.
17.
YounJGulveEAHolloszyJO: Calcium stimulates glucose transport in skeletal muscle by a pathway independent of contractionAm J Physiol1991, 260:C555–C561.
18.
YoungDAWallberg-HenrikssonHSleeperMDHolloszyJO: Reversal of the exercise-induced increase in muscle permeability to glucoseAm J Physiol1987, 253:E331–E335.
19.
GulveEACarteeGDZierathJRCorpusVMHolloszyJO: Reversal of enhanced muscle glucose transport after exercise: Roles of insulin and glucoseAm J Physiol1990, 259:E685–E691.
FluckeyJDHickeyMSBrambrinkJKHartKKAlexanderKCraigBW: Effects of resistance exercise on glucose tolerance in normal and glucose-intolerant subjectsJ Appl Physiol1994, 77:1087–1092. Seventeenparticipants performed resistance exercise (a 3-set of 10-repetition protocol on seven different strength-training machines). Forty-eight hours before and 18 h after this lifting protocol, oral glucose tolerance tests were administered. The total insulin responses (area under the curve) were significantly lower after exercise. C-peptide levels after exercise were unchanged, indicating that the lower insulin response was a result of an enhanced ability to clear insulin from the blood.
22.
PriceTBRothmanDLTaylorRAvisonMJShulmanGIShulmanRG: Human muscle glycogen resynthesis after exercise: Insulin-dependent and -independent phasesJ Appl Physiol1994, 76:104–111. Single-leg toe raises were performed by 12 untrained volunteers to deplete the glycogen content in the gastrocnemius muscle to 75, 50 or 25% of resting concentrations. The insulin dependence of glycogen synthesis was assessed with and without an infusion of somatostatin designed to inhibit insulin secretion. The results indicate that after depleting glycogen concentrations below 30 mmol/l, resynthesis is insulin-independent and glycogen-dependent, which suggests local control.
23.
HenrikssonJHicknerRC: Training-induced adaptations in skeletal muscle In Oxford Textbook of Sports Medicine. Edited by HarriesMMicheliLStanishWDWilliamsC.Oxford: Oxford University Press; 1994:27–45.
24.
BjörntorpPFahlénMGrimbyGGustafsonAHolmJRenströmP: Carbohydrate and lipid metabolism in middle-aged physically well-trained menMetabolism1972, 21:1037–1044.
25.
LohmannDLieboldFHeilmannWSebgerHPahlA: Diminished insulin response in highly trained athlethesMetabolism1978, 5:521–524.
26.
WirthADiehmCMayerHMörlHVogelIBjörntorpP: Plasma C-peptide and insulin in trained and untrained subjectsJ Appl Physiol1981, 50:71–77.
27.
YoungJCEnslinJKucaB: Exercise intensity and glucose tolerance in trained and nontrained subjectsJ Appl Physiol1989, 67:39–43.
HeathGWGavinJRIIIHinderliterJMHagbergJMBloomfieldSAHolloszyJO: Effects of exercise and lack of exercise on glucose tolerance and insulin sensitivityJ Appl Physiol1983, 55:512–517.
30.
CononieCCGoldbergAPRogusEHagbergJM: Seven consecutive days of exercise lowers plasma insulin responses to an oral glucose challenge in sedentary elderlyJ Am Geriatr Soc1994, 42:394–398.
31.
KingDSBaldusPJSharpRLKeslLDFeltmeyerTLRiddleMS: Time-course for exercise-induced alterations in insulin action and glucose tolerance in middle-aged peopleJ Appl Physiol1995, 78:17–22. Ninemoderately trained middle-aged participants exercised for 45 min at 73% VO2max for 5 days, followed by 7 days of inactivity. Oral glucose tolerance tests were performed immediately after the final exercise bout and 1, 3, 5 and 7 days after exercise. The data showed an exaggerated insulin response and a marked impairment of insulin action immediately after exercise. This transient insulin resistance was replaced within 24 h by enhanced insulin action and a reduced insulin response, which persisted for 3 but not 5 days.
32.
NuutilaPKnuutiJHeinonenORuotsalainenUTeräsMBergmanJ: Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscleJ Clin Invest1994, 93:2267–2274. Ratesof glucose uptake were compared in the skeletal muscles of seven trained and seven untrained individuals during a 2 h euglycaemic hyperinsulinaemic clamp test using [18F]-fluoro-2-deoxy-D-glucose and positron emission tomography. Whole-body glucose uptake in the athletes increased by 68%, by 99% in femoral muscles and by 62% in arm muscles.
33.
MikinesKJSonneBTronierBGalboH: Effects of acute exercise and detraining on insulin action in trained menJ Appl Physiol1989, 66:704–711.
34.
DelaFMikinesKJvon LinstowMSecherNHGalboH: Effect of training on insulin-mediated glucose uptake in human muscleAm J Physiol1992, 263:E1134–E1143. Insulinsensitivity was studied in seven sedentary young participants 16 h after the last training session of a 10-week programme of one-leg training. The glucose uptake (determined as leg blood flow times the arterio-venous glucose difference) during a euglycaemic clamp test at a physiological insulin level was 30% higher in the trained than in the untrained leg, and a single exercise bout did not influence the insulin sensitivity of the untrained leg. The adaption in the trained leg had disappeared 6 days after the last exercise session.
35.
MillerJPPratleyREGoldbergAPGordonPRubinMTreuthMS: Strength training increases insulin action in healthy 50- to 65-year-old menJ Appl Physiol1994, 77:1122–1127.
36.
SmutokMAReeceCKokkinosPFFarmerCMDawsonPKDeVaneJ: Effects of exercise training modality on glucose tolerance in men with abnormal glucose regulationInt J Sports Med1994, 15:283–289.
37.
HerseyWCIIIGravesJEPollockMLGingerichRShiremanRBHeathGW: Endurance exercise training improves body composition and plasma insulin responses in 70- to 79-year-old men and womenMetabolism1994, 43:847–854.
38.
MillerWJShermanWMIvyJL: Effect of strength training on glucose tolerance and post-glucose insulin responseMed Sci Sports Exerc1984, 16:539–543.
39.
ShriverTCSchaulisDLThompsonSRSharpRLKingDS: Effects of exercise intensity on glucose tolerance and insulin sensitivity [abstract]Med Sci Sports Exerc1993, 25:S76.
40.
BraunBZimmermanMBKretchmerN: Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitusJ Appl Physiol1995, 78:300–306.
41.
HolmängASvedbergJJennischeEBjörntorpP: Effects of testosterone on muscle insulin sensitivity and morphology in female ratsAm J Physiol1990, 259:E555–E560. Nineteenrats underwent oophorectomy and 15 had a sham operation. Thereafter, nine of the former and six of the latter rats were given 2 mg intramuscular testosterone-depot every second week for 12 weeks. Glycogen synthesis and 2-deoxy-D-glucose uptake during a euglycaemic clamp were reduced by 50% with testosterone in all muscles studied. This decrease correlated with the observed reduction in the percentage of type-1 fibres and muscle capillarization.
42.
HolmängALarssonB-MBrzezinskaZBjörntorpP: Effects of short-term testosterone exposure on insulin sensitivity of muscles in female ratsAm J Physiol1992, 262:E851–E855.
43.
KatzMSLowenthalDT: Influences of age and exercise on glucose metabolism: Implications for management of older diabeticsSouth Med J1994, 87:S70–S73.
44.
DevlinJT: Effects of exercise on insulin sensitivity in humansDiabetes Care1992, 15:1690–1693.
45.
SchneiderSHAmorosaLFKhachadurianAKRudermanNB: Studies on the mechanism of improved glucose control during regular exercise in type-2 (non-insulin-dependent) diabetesDiabetologia1984, 26:355–360.
46.
DelaFPlougTHandbergAPetersenLNLarsenJJMikinesKJ: Physical training increases muscle GLUT-4 protein and mRNA in patients with NIDDMDiabetes1994, 43:862–865.
47.
EbelingPBoureyRKoranyiLTuominenJAGroopLCHenrikssonJ: Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (glut-4) concentraion, and glycogen synthase activityJ Clin Invest1993, 92:1623–1631. Whole-body glucose disposal during a euglycaemic hyperinsulinaemic (100 μU/ml) clamp was studied in nine well-trained male athletes and in ten untrained controls. Whole-body glucose disposal was 32% higher and non-oxidative glucose disposal 62% higher in the athletes than in the controls. This increase correlated with increases in the concentration of muscle glucose transport protein (GLUT-4), glycogen synthase activity and forearm blood flow.
48.
RenJ-MSemenkovichCFGulveEAGaoJHolloszyJO: Exercise induces rapid increases in GLUT-4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscleJ Biol Chem1994, 269:14396–14401. Ratsexercised by swimming for two 3 h bouts separated by a 45 min rest period. Some rats performed this exercise programme once, and others a second time after a 16 h rest period. Sixteen hours after the last bout of exercise the epitrochlearis muscles were dissected out. After one bout of exercise the expression of GLUT-4 protein increased by 50% and after the second bout increased further to 100% above the baseline level. Glucose transport activity, maximally stimulated by insulin, contractions or hypoxia, increased roughly in proportion to the adaptive increase in the GLUT-4 protein in epitrochlearis muscles.
49.
HoumardJAHortobágyiTNeuferPDAnderson JohnsRFraserDDIsraelRG: Training cessation does not alter GLUT-4 protein levels in human skeletal muscleJ Appl Physiol1993, 74:776–781. Twelveendurance- and 12 strength-trained individuals were examined during normal training and after 14 days of rest. Insulin sensitivity (oral glucose tolerance test) and the oxidative capacity of muscle were significantly reduced during the extended period of rest. GLUT-4 content, on the other hand, was unaltered.
50.
KongXManchesterJSalmonsSLawrenceJCJr: Glucose transporters in single skeletal muscle fibersJ Biol Chem1994, 269:12963–12967. Theamount of the glucose transporter isoform GLUT-4, measured by immunoblotting, was determined in single fibres of identified type dissected from rabbit skeletal muscle. Under chronic electrical stimulation (10 Hz), the GLUT-4 level changed in parallel with hexokinase activity: Both increased by 2.5 times after 1 day and by 14 times after 21 days.
51.
HenriksenEJRodnickKJMondonCEJamesDEHolloszyJO: Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscleJ Appl Physiol1991, 70:2322–2327.
52.
HolloszyJOCoyleEF: Adaptations of skeletal muscle to endurance exercise and their metabolic consequencesJ Appl Physiol1984, 56:831–838.
53.
SumidaKDDonovanCM: Endurance training fails to inhibit skeletal muscle glucose uptake during exerciseJ Appl Physiol1994, 75:1876–1881.
54.
CogganARKohrtWMSpinaRJBierDMHolloszyJO: Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in menJ Appl Physiol1990, 68:990–996.
55.
VestergaardHAndersenPHLundSSchmitzOJunkerSPedersenO: Pre- and posttranslational upregulation of muscle-specific glycogen synthase in athletesAm J Physiol1994, 266:E92–E101. Totalglycogen synthase activity and its half-maximal activation by glucose-6-phosphate were 34 and 50% higher, respectively, in seven endurance athletes than in eight controls. The authors concluded that this difference is an important cause of the observed difference in the glucose disposal rate during a euglycaemic clamp test.
56.
DelaFHandbergAMikinesKJVintenJGalboH: GLUT 4 and insulin receptor binding and kinase activity in trained human muscleJ Physiol1993, 469:615–624.
HolmängABjörntorpPRippeB: Tissue uptake of insulin and inulin in red and white skeletal muscle in vivoAm J Physiol1992, 263:H1–H7. Aeuglycaemic hyperinsulinaemic clamp was maintained for 2 h in 63 rats. During this period bolus doses of [125I]-(Tyr A 14) human insulin, [131I]-human serum albumin, unlabelled human serum albumin and [14C]-inulin were injected. The kinetics of the plasma-interstitial equilibration of these radiolabelled compounds were followed in four muscles of differing capillarity. The distribution volume at time 0 for insulin was found to be five times larger than the plasma volume in [START]each muscle sample, indicating a high degree of insulin binding to structures within the vascular compartment, conceivably to the vascular endothelium.
59.
LaaksoMEdelmanSVBrechtelGBaronAD: Decreased effect of insulin to stimulate skeletal muscle blood flow in obese manJ Clin Invest1990, 85:1844–1852. Duringa euglycaemic hyperinsulinaemic clamp over a large range of serum insulin concentrations, the insulin concentration needed to increase leg blood flow (thermodilution technique) to half the maximal value was approximately fourfold higher in six obese than in six lean men.
60.
AndersenPHenrikssonJ: Capillary supply of the quadriceps femoris muscle of man: Adaptive response to exerciseJ Physiol1977, 270:677–690.
61.
EbelingPKoivistoVA: Non-esterified fatty acids regulate lipid and glucose oxidation and glycogen synthesis in healthy manDiabetologia1994, 37:202–209.
62.
PoehlmanETRosenCJCopelandKC: The influence of endurance training on insulin-like growth factor-1 in older individualsMetabolism1994, 43:1401–1405.
