Exercise Training Improves Insulin-Mediated Capillary Recruitment in Association With Glucose Uptake in Rat Hindlimb

Rattigan, Stephen; Wallis, Michelle G.; Youd, Joanne Maree; Clark, Michael G.

doi:10.2337/diabetes.50.12.2659

Cited by 57 publications

(50 citation statements)

References 31 publications

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“…This method does not allow for a distinction between nutritive and non-nutritive flow, and thus it cannot be directly evaluated if delivery of bloodborne substrates at the cellular level is improved by training as demonstrated in rodents (12). We observe that total venous blood flow is higher in the trained thigh (Fig.…”

Section: Discussionmentioning

confidence: 68%

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Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle

et al. 2007

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The purpose of this study was to investigate the mechanisms explaining improved insulin-stimulated glucose uptake after exercise training in human skeletal muscle. Eight healthy men performed 3 weeks of one-legged knee extensor endurance exercise training. Fifteen hours after the last exercise bout, insulin-stimulated glucose uptake was ϳ60% higher (P < 0.01) in the trained compared with the untrained leg during a hyperinsulinemic-euglycemic clamp. Muscle biopsies were obtained before and after training as well as after 10 and 120 min of insulin stimulation in both legs. Protein content of Akt1/2 (55 ؎ 17%, P < 0.05), AS160 (25 ؎ 8%, P ‫؍‬ 0.08), GLUT4 (52 ؎ 19%, P < 0.001), hexokinase 2 (HK2) (197 ؎ 40%, P < 0.001), and insulin-responsive aminopeptidase (65 ؎ 15%, P < 0.001) increased in muscle in response to training. During hyperinsulinemia, activities of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-K) (P < 0.005), Akt1 (P < 0.05), Akt2 (P < 0.005), and glycogen synthase (GS) (percent I-form, P < 0.05) increased similarly in both trained and untrained muscle, consistent with increased phosphorylation of Akt Thr 308 , Akt Ser 473 , AS160, glycogen synthase kinase (GSK)-3␣ Ser 21 , and GSK-3␤ Ser 9 and decreased phosphorylation of GS site 3a؉b (all P < 0.005). Interestingly, training improved insulin action on thigh blood flow, and, furthermore, in both basal and insulin-stimulated muscle tissue, activities of Akt1 and GS and phosphorylation of AS160 increased with training (all P < 0.05). In contrast, training reduced IRS-1-associated PI3-K activity (P < 0.05) in both basal and insulin-stimulated muscle tissue. Our findings do not support generally improved insulin signaling after endurance training; rather it seems that improved insulin-stimulated glucose uptake may result from hemodynamic adaptations as well as increased cellular protein content of individual insulin signaling components and molecules involved in glucose transport and metabolism.

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Section: Discussionmentioning

confidence: 68%

“…Skeletal muscle adaptations to training are multiple, including improved hemodynamic effects of insulin (7,12). Furthermore, exercise training results in changes in expression and/or activity of proteins involved in glucose uptake/metabolism in both rodent (13,14) and human skeletal muscle (2,(15)(16)(17).…”

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confidence: 99%

Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle

et al. 2007

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“…Previously, this relationship has been described for ␣-methyl serotonin (34), TNF-␣ (35), and exercise-trained rats (40). A recurring correlation between IMGU and insulin-mediated capillary recruitment implies but does not necessarily prove causality.…”

Section: Discussionmentioning

confidence: 99%

Lipid Infusion Impairs Physiologic Insulin-Mediated Capillary Recruitment and Muscle Glucose Uptake In Vivo

2002

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Infusion of triglycerides and heparin causes insulin resistance in muscle. Because the vascular actions of insulin, particularly capillary recruitment, may contribute to the increase in glucose uptake by skeletal muscle, we investigated the effects of Intralipid/heparin infusion on the hemodynamic actions of insulin during clamp conditions. Saline or 10% Intralipid/heparin (33 U/ml) was infused into anesthetized rats at 20 l/min for 6 h. At 4 h into the saline infusion, a 2-h hyperinsulinemic (3 mU ⅐ min ؊1 ⅐ kg ؊1 )-euglycemic clamp was conducted (Ins group). At 4 h into the lipid infusion, a 2-h saline control (Lip group) or 2-h hyperinsulinemiceuglycemic clamp (Lip ؉ Ins group) was conducted. Arterial blood pressure, heart rate, femoral blood flow (FBF), hindleg vascular resistance, glucose infusion rate (GIR), hindleg glucose uptake (HGU), and muscle 2-deoxyglucose uptake (Rg) were measured. Capillary recruitment, as measured by metabolism of infused 1-methylxanthine (1-MX), was also assessed. When compared with either Lip or Lip ؉ Ins, Ins had no effect on arterial blood pressure, heart rate, FBF, or vascular resistance but increased GIR, HGU, and Rg of soleus, plantaris, extensor digitorum longus, and gastrocnemius red muscles and hindlimb 1-MX metabolism. GIR, HGU, and Rg of soleus, plantaris, gastrocnemius red, and the combined muscles and 1-MX metabolism were less in Lip ؉ Ins than in Ins rats. HGU correlated closely with hindleg capillary recruitment (r ‫؍‬ 0.86, P < 0.001) but not total hindleg blood flow. In conclusion, acute elevation of plasma free fatty acids blocks insulinmediated glucose uptake and capillary recruitment.

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“…These findings suggest that the stimulation of capillary recruitment by methacholine is independent of and additive to that of insulin, but as pointed out above, likely to be engaging receptors in the same locality of the microvasculature. It is perhaps pertinent to note that voluntary exercise-training of our rats also augmented insulin-mediated capillary recruitment and insulin-mediated glucose uptake by muscle [29].…”

Section: Discussionmentioning

confidence: 99%

Local methacholine but not bradykinin potentiates insulin-mediated glucose uptake in muscle in vivo by augmenting capillary recruitment

et al. 2004

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Aims/hypothesis. Insulin has nitric-oxide-dependent vasodilatory effects in muscle, including capillary recruitment, that enhance access for itself and glucose. However, nitric-oxide-dependent vasodilators other than methacholine do not enhance insulin action. Our hypothesis is that methacholine, unlike bradykinin, enhances insulin-mediated glucose uptake in muscle by augmenting capillary recruitment. Methods. Local infusion of either methacholine or bradykinin into one leg of the anaesthetised rat was made during physiological insulin (3 mU·kg −1 ·min −1 ) infusion under euglycaemic conditions and without affecting systemic blood pressure. Whole-body glucose infusion was determined, as was femoral blood flow, 2-deoxyglucose uptake into calf muscles and the metabolism of infused 1-methylxanthine, a measure of capillary recruitment for each leg. Results. Methacholine alone (0.3 µmol·l -1 ) increased femoral arterial blood flow, increased capillary recruitment but had no effect on 2-deoxyglucose uptake of the test leg relative to the contra-lateral control leg. Insulin alone (systemically) required a glucose infusion rate of 8.7 mg·kg −1 ·min −1 to maintain euglycaemia, increased 2-deoxyglucose uptake and capillary recruitment, but was without effect on femoral blood flow in either leg. Local methacholine with systemic insulin infusion increased femoral blood flow, 2-deoxyglucose uptake and capillary recruitment in the test leg only. Bradykinin (0.07 µmol·l -1 ), alone or with insulin, administered in a manner that increased femoral blood flow similarly to methacholine, did not affect 2-deoxyglucose uptake or capillary recruitment. Conclusions/interpretation. Methacholine but not bradykinin enhances insulin-mediated muscle glucose uptake in vivo. We conclude that methacholine acts at specific sites in the vasculature of muscle to stimulate capillary recruitment and thereby enhance insulin access.Keywords Global vasodilatation in muscle · Insulin and glucose delivery to muscle · Muscle blood flow · Specific regional vasodilatation in muscle.

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Exercise Training Improves Insulin-Mediated Capillary Recruitment in Association With Glucose Uptake in Rat Hindlimb

Cited by 57 publications

References 31 publications

Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle

Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle

Lipid Infusion Impairs Physiologic Insulin-Mediated Capillary Recruitment and Muscle Glucose Uptake In Vivo

Local methacholine but not bradykinin potentiates insulin-mediated glucose uptake in muscle in vivo by augmenting capillary recruitment

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