Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes.

Kennedy, J W; Hirshman, Michael F.; Gervino, Ernest V.; Ocel, J.; Ra, Forse; Hoenig, S; Aronson, Doron; Goodyear, Laurie J.; Horton, Edward S.

doi:10.2337/diabetes.48.5.1192

Cited by 340 publications

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“…Together with the present results obtained in ovine M. semimembranosus, which comprises predominantly type II muscle fibers (1,32), this suggests that the lack of exercise effect on insulin-stimulated Akt serine phosphorylation is common to different muscle fiber types. Repeated muscle biopsies, as conducted in this study in sheep, have similarly been used in human studies to investigate the mechanisms underlying exercise responses in this tissue, including in diabetes (e.g., 27,33,46,55). In addition to muscle, it is possible to repeatedly biopsy fat (29) and liver (24) in sheep, which would permit longitudinal studies of exercise responses in multiple tissues in future studies in this species, as well as to investigate responses in other tissues, such as pancreas and heart at post mortem.…”

Section: Discussionmentioning

confidence: 99%

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

McConell

Kaur

Falcão-Tebas

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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In healthy humans and rodents, chronic and acute exercise improves subsequent insulin sensitivity of skeletal muscle. A large animal species with similar metabolic responses to exercise would permit longitudinal studies, including repeated biopsies of muscle and other tissues not possible in rodents, and enable study of interactions with insulin-resistant physiological states not feasible in humans. Therefore, we examined whether acute exercise increases insulin sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp (HEC) in mature female sheep (n ϭ 7). Sheep were familiarized to treadmill walking and then performed an acute exercise bout (30 min, 8% slope, up to 4.4 km/h). A second HEC was conducted ϳ18 h after the acute exercise. Musculus semimembranosus biopsies were obtained before and after each HEC. Glucose infusion rate during the HEC increased 40% (P ϭ 0.003) and insulin sensitivity (glucose infusion rate/plasma insulin concentration) increased 32% (P ϭ 0.028) after acute exercise. Activation of proximal insulin signaling in skeletal muscle after the HEC, measured as Ser 473 phosphorylation of Akt, increased approximately five-fold in response to insulin (P Ͻ 0.001) and was unaltered by acute exercise performed 18 h earlier. PGC1␣ and GLUT4 protein, glycogen content and citrate synthase activity in skeletal muscle did not change in response to insulin or exercise. In conclusion, improved insulin sensitivity and unchanged proximal insulin signaling on the day after acute exercise in sheep are consistent with responses in humans and rodents, suggesting that the sheep is an appropriate large-animal model in which to study responses to exercise. exercise; insulin sensitivity; muscle; sheep REGULAR EXERCISE TRAINING increases insulin-stimulated whole body and skeletal muscle glucose uptake in humans, in healthy individuals as well as in those who have Type 2 diabetes (T2D) or are obese or aged (reviewed by Refs. 14, 31, 45). Increased expression of hexokinase 2, some insulin signaling proteins and GLUT4, and greater insulin-induced vasodilation are implicated as mechanisms for enhanced insulin-stimulated glucose uptake after training (14,31,45). Exercise training probably acts mainly at distal sites to increase glucose uptake, with the balance of evidence, suggesting that proximal insulin signaling is not upregulated (14, 38). Importantly, a single bout of exercise also increases the insulin sensitivity of glucose uptake during the following 4 -48 h in healthy humans (34,46,52,54,55). Similar effects have been demonstrated in rodents, where an acute exercise bout increases in vitro insulin-stimulated glucose uptake in mouse muscle 85 min after exercise (18) and in rat muscle collected 3-16 h after a single bout of exercise (8,15,19,43,44). Available evidence from studies in humans and rodents suggests that acute exercise, like exercise training, increases insulin sensitivity without changes in proximal insulin signaling (reviewed in Ref. 31).A large animal model with...

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Section: Discussionmentioning

confidence: 99%

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

McConell

Kaur

Falcão-Tebas

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…This mechanism may explain the enhanced sensitivity to insulin observed in physically active DM patients [11,13,16,22,24,26]. Increased mass in skeletal muscle, enhanced blood flow in muscle, greater density of insulin receptors, enhanced disposal of glucose in skeletal muscle, and a reduction in body fat could also contribute to this insulin sensitivity and improved glucose tolerance induced by physical training in DM patients [25,49].…”

Section: Physical Exercise In Diabetic Patientsmentioning

confidence: 99%

“…As mentioned above, the aim of exercise in type II diabetic patients is to induce acute and chronic physiological changes, which improve insulin sensitivity and glucose tolerance [11,13,22,23,24,26]. To maintain glucose homeostasis, glucagon and adrenalin are released during acute exercise, which increases hepatic glucose production; simultaneously, the insulin secretion by pancreatic b cells is reduced [37,40,52].…”

Section: Physical Exercise In Diabetic Patientsmentioning

confidence: 99%

“…During fasting, the physiological blood concentrations of glucose are maintained by the liver. In the postprandial state, the rise in blood glucose concentration stimulates insulin secretion, which reduces hepatic glucose production and increases membrane glucose transporters (GLUT) in peripheral tissues, thus reducing blood glucose [11,13,24,26].…”

Section: Physical Exercise In Diabetic Patientsmentioning

confidence: 99%

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Regular physical exercise in patients with type II diabetes mellitus

Nakhanakhup

Moungmee

Appell

et al. 2006

Eur. Rev. Aging.Phys. Act.

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It is widely accepted that regular physical exercise helps diabetic patients control blood glucose, reduce cardiovascular risk factors, and prevent other related complications. In spite of the undoubted benefits of regular physical exercise, diabetic patients with chronic complications should be aware of potential hazards of practicing exercise. To avoid some harmful consequences of acute exercise, it is necessary to adopt a vigilant attitude with these risk patients and to carefully adjust type and intensity of exercise to the individual situation. This article intends to summarize and analyze the current literature concerning the preventive and therapeutic effects of regular exercise in diabetic patients, pointing out its physiological influence on blood glucose regulation, and to analyze the potential risks of acute physical exercise and the precautions given to patients with a variety of complications.

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“…Both mechanisms increase glucose uptake via translocation of solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4), from the cytosol of the muscle cell to the plasma membrane and ttubules. Patients with type 2 diabetes [1] and insulin-resistant obese Zucker rats [2] have impaired insulin-stimulated SLC2A4 translocation; however, exercise-stimulated SLC2 A4 translocation is normal [3,4]. The signalling pathways through which these distinct mechanisms operate differ [5].…”

Section: Introductionmentioning

confidence: 99%

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

et al. 2005

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Aims/hypothesis: Nitric oxide (NO) has been implicated as an important signalling molecule in the contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control. The current study sought to determine whether acute infusion of the NO donor, sodium nitroprusside (SNP), increases leg glucose uptake at rest in patients with type 2 diabetes. Methods: Fifteen male patients with type 2 diabetes (aged 54±4 years, mean±SD) were entered into a randomised, cross-over design study, examining the effect of a 30-min intra-femoral infusion of SNP on leg glucose uptake. Comparison was made with a 30-min infusion of verapamil, titrated to elicit similar leg blood flow responses to SNP. Leg blood flow was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of leg blood flow and the femoral arterio-venous (A-V) glucose concentration gradient. Results: The two drugs increased leg blood flow to a similar extent (p= 0.50). Both leg A-V glucose concentration gradient (SNP 0.12±0.05, verapamil −0.06±0.04 mmol/l; mean±SEM, p=0.03) and leg glucose uptake (SNP 0.17±0.09, verapamil −0.09±0.06 mmol/min; p=0.03) were higher with the SNP treatment than with verapamil. These results occurred independently of any significant difference in plasma insulin concentration between drugs (p=0.56). Conclusions/interpretation: Acute infusion of SNP resulted in greater glucose uptake relative to verapamil. NO may therefore be an important mediator of peripheral glucose disposal and a potential therapeutic target in patients with type 2 diabetes.

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Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes.

Cited by 340 publications

References 0 publications

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

Acute exercise increases insulin sensitivity in adult sheep: a new preclinical model

Regular physical exercise in patients with type II diabetes mellitus

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

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