Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects

Christ-Roberts, Christine Y.; Pratipanawatr, Thongchai; Pratipanawatr, Wilailak; Berria, Rachele; Belfort, Renata; Kashyap, Sangeeta R.; Mandarino, Lawrence J.

doi:10.1016/j.metabol.2004.03.022

Cited by 169 publications

(173 citation statements)

References 41 publications

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“…8) increased with training as observed in both basal and insulin-stimulated muscle. This adaptation has previously been observed in response to both strength and endurance training regimens (2,44). However, in contrast to the study by Holten et al (2), no detectable significant change in protein expression of GS was observed in the present study.…”

contrasting

confidence: 64%

“…Furthermore, it has been shown that insulin-stimulated phosphotyrosine-associated PI3-K activity is greater after 7 days of endurance training in young (18) but not in middle-aged obese (19,43) or type 2 diabetic subjects (43). In contrast, in response to 8 weeks of endurance training, IRS-1-associated PI3-K activity was ϳ20% lower in basal and insulin-stimulated trained muscle of elderly type 2 diabetic patients and corresponding control subjects (44), although this was only significant in basal samples of the control subjects. Thus, the adaptations at the level of PI3-K may depend on the length of the exercise training regimen and subject characteristics.…”

Section: Discussionmentioning

confidence: 98%

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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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contrasting

confidence: 64%

Section: Discussionmentioning

confidence: 98%

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

et al. 2007

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“…Several studies suggest that exercise increases the protein GLUT4 and mRNA expression, and it has been used as a method for diabetes treatment (9)(10)(11). Muscle contraction can stimulate glucose transport by a pathway independent of the insulin signaling (12), indicating that a person who presents impaired insulin signaling pathway can improve glucose homeostasis by means of exercise training (13).…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke exposure severely reduces peripheral insulin sensitivity without changing GLUT4 expression in oxidative muscle of Wistar rats

Ebersbach-Silva

Alves

Fonseca

et al. 2013

Arq Bras Endocrinol Metab

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Objective: To evaluate the effect of exposure to cigarette smoke and running training on a treadmill on the expression of glucose transporter GLUT4 in oxidative soleus muscle of rats. Materials and methods: Wistar rats were divided into: (C) control, (E) exercise control, (SS), sedentary smoker, and (ES) exercise smoker. Insulin Tolerance Test, Western blotting, and RT--PCR were performed for the evaluation of GLUT4 levels. Results: The SS group presented lower insulin sensitivity with reduced GLUT4 protein in the plasma membrane (PM), no changes in the microsomal fraction, but increased mRNA content. Training reversed this condition. No intervention altered total GLUT4 content of the oxidative muscle. Conclusion: These results suggest that passive smoking stimulates GLUT4 transcription without changing total protein content, but impairs the ability of GLUT4 translocation to the PM. On the other hand, training seems to reduce the deleterious effects, even under the influence of cigarette smoking. Arq Bras Endocrinol Metab. 2013;57(1):19-26 Keywords Cigarette smoking; training; glucose transporter; GLUT4; insulin resistance; oxidative muscle RESUMO Objective: Avaliar o efeito da exposição à fumaça de cigarro e do treinamento de corrida em esteira rolante sobre a expressão do transportador de glicose GLUT4 no músculo oxidativo solear de ratos. Materiais e métodos: Ratos Wistar foram divididos em: (C) controle, (E) exercitado, (SS) fumante sedentário e (ES) fumante exercitado. Foram realizados testes de tolerância à insulina, Western Blotting e RT-PCR para avaliação da expressão de GLUT4. Resultados: O grupo SS apresentou menor sensibilidade à insulina, com redução de proteína GLUT4 na membrana plasmática (MP), sem alteração na fração microssomal, e conteúdo de RNAm aumentado. O treinamento reverteu esse quadro. Nenhuma intervenção alterou o conteúdo total de GLUT4 no músculo oxidativo. Conclusão: Esses resultados sugerem que o fumo estimula a transcrição de GLUT4 sem alterar o conteúdo total de proteína, porém prejudica a capacidade de translocação para a MP. Já o treinamento em esteira parece, mesmo sob influência do cigarro, reduzir seus efeitos deletérios. Arq Bras Endocrinol Metab. 2013;57(1):19-26 Descritores

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“…For instance, in type 2 diabetes, adaptations that affect glucose homeostasis are of great importance. As reviewed by Ivy, 147 a series of changes (independent of changes in body mass 64 ) occur as a result of regular physical activity, including increased glycogen synthase 148 and hexokinase activity, 149 increased GLUT-4 protein and mRNA expression, 148,150 and improved muscle capillary density (resulting in improved glucose delivery to the muscle).…”

mentioning

confidence: 99%

Health benefits of physical activity: the evidence

Warburton¹

2006

Canadian Medical Association Journal

6,031

4,137

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P hysical inactivity is a modifiable risk factor for cardiovascular disease and a widening variety of other chronic diseases, including diabetes mellitus, cancer (colon and breast), obesity, hypertension, bone and joint diseases (osteoporosis and osteoarthritis), and depression.1-14 The prevalence of physical inactivity (among 51% of adult Canadians) is higher than that of all other modifiable risk factors. 15 In this article we review the current evidence relating to physical activity in the primary and secondary prevention of premature death from any cause, cardiovascular disease, diabetes, some cancers and osteoporosis. We also discuss the evidence relating to physical fitness and musculoskeletal fitness and briefly describe the independent effects of frequency and intensity of physical activity. (A glossary of terms related to the topic appears in Appendix 1). In a companion paper, to be published in the Mar. 28 issue, we will review how to evaluate the healthrelated physical fitness and activity levels of patients and will provide exercise recommendations for health.Several authors have attempted to summarize the evidence in systematic reviews and meta-analyses. These evaluations are often overlapping (reviewing the same evidence). Some of the most commonly cited cohorts have been described in different studies over time as more data accumulate (see Appendix 2, available online at www.cmaj.ca/cgi/content/full/174/6 /801/DC1). In this review, we searched the literature using the key words "physical activity," "health," "health status," "fitness," "exercise," "chronic disease," "mortality" and diseasespecific terms (e.g., "cardiovascular disease," "cancer," "diabetes" and "osteoporosis"). Using our best judgment, we selected individual studies that were frequently included in systematic reviews, consensus statements and meta-analyses and considered them as examples of the best evidence available. We also have included important new findings regarding the relation between physical activity and fitness and allcause and cardiovascular-related mortality. All-cause and cardiovascular-related death Primary preventionSince the seminal work of Morris and colleagues in the 1950s16,17 and the early work of Paffenbarger and colleagues in the 1970s, 18,19 there have been numerous long-term prospective follow-up studies (mainly involving men but more recently women also) that have assessed the relative risk of death from any cause and from specific diseases (e.g., carciovascular disease) associated with physical inactivity. 6,20-26Both men and women who reported increased levels of physical activity and fitness were found to have reductions in relative risk (by about 20%-35% 27,28) of death (see Appendix 2, available at www.cmaj.ca/cgi/content/full/174/6/801/DC1). For example, in a study involving healthy middle-aged men and women followed up for 8 years, the lowest quintiles of physical fitness, as measured on an exercise treadmill, were associated with an increased risk of death from any cause compared with the top quin...

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Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects

Cited by 169 publications

References 41 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

Cigarette smoke exposure severely reduces peripheral insulin sensitivity without changing GLUT4 expression in oxidative muscle of Wistar rats

Health benefits of physical activity: the evidence

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