Insulin resistance: vascular function and exercise

Moon-Hyon Hwang, Sewon Lee, Moon-Hyon Hwang, Sewon Lee

Abstract

Insulin resistance associated with metabolic syndrome and Type 2 diabetes mellitus is an epidemic metabolic disorder, which increases the risk of cardiovascular complications. Impaired vascular endothelial function is an early marker for atherosclerosis, which causes cardiovascular complications. Both experimental and clinical studies indicate that endothelial dysfunction in vasculatures occurs with insulin resistance. The associated physiological mechanisms are not fully appreciated yet, however, it seems that augmented oxidative stress, a physiological imbalance between oxidants and antioxidants, in vascular cells is a possible mechanism involved in various vascular beds with insulin resistance and hyperglycemia. Regardless of the inclusion of resistance exercise, aerobic exercise seems to be beneficial for vascular endothelial function in both large conduit and small resistance vessels in both clinical and experimental studies with insulin resistance. In clinical cases, aerobic exercise over 8 weeks with higher intensity seems more beneficial than the cases with shorter duration and lower intensity. However, more studies are needed in the future to elucidate the physiological mechanisms by which vascular endothelial function is impaired in insulin resistance and improved with aerobic exercise.

Keywords: aerobic exercise; atherosclerosis; diabetes mellitus; metabolic syndrome; resistance exercise.

References

    1. American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care. 2008;31(Suppl 1):S55–S60.
    1. Hwang M.H., Kim S. Type 2 Diabetes: endothelial dysfunction and exercise. J Exerc Nutrit Biochem. 2014;18:239–247.
    1. Alberti K.G., Zimmet P., Shaw J. Group IDFETFC. The metabolic syndrome—a new worldwide definition. Lancet. 2005;366:1059–1062.
    1. Mozumdar A., Liguori G. Persistent increase of prevalence of metabolic syndrome among U.S. adults: NHANES III to NHANES 1999-2006. Diabetes Care. 2011;34:216–219.
    1. Lim S., Shin H., Song J.H., Kwak S.H., Kang S.M., Yoon Y.J. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998-2007. Diabetes Care. 2011;34:1323–1328.
    1. Davidson M.B. Metabolic syndrome/insulin resistance syndrome/pre-diabetes: new section in diabetes care. Diabetes Care. 2003;26:3179.
    1. Despres J.P., Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881–887.
    1. Ostergard T., Nyholm B., Hansen T.K., Rasmussen L.M., Ingerslev J., Sorensen K.E. Endothelial function and biochemical vascular markers in first-degree relatives of type 2 diabetic patients: the effect of exercise training. Metab Clin Exp. 2006;55:1508–1515.
    1. Furukawa S., Fujita T., Shimabukuro M., Iwaki M., Yamada Y., Nakajima Y. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–1761.
    1. Bonetti P.O., Lerman L.O., Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol. 2003;23:168–175.
    1. Wellen K.E., Hotamisligil G.S. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111–1119.
    1. Grattagliano I., Vendemiale G., Boscia F., Micelli-Ferrari T., Cardia L., Altomare E. Oxidative retinal products and ocular damages in diabetic patients. Free Radic Biol Med. 1998;25:369–372.
    1. Stocker R., Keaney J.F., Jr Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84:1381–1478.
    1. Tjonna A.E., Rognmo O., Bye A., Stolen T.O., Wisloff U. Time course of endothelial adaptation after acute and chronic exercise in patients with metabolic syndrome. J Strength Condit Res. 2011;25:2552–2558.
    1. Tjonna A.E., Lee S.J., Rognmo O., Stolen T.O., Bye A., Haram P.M. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation. 2008;118:346–354.
    1. Montero D., Walther G., Benamo E., Perez-Martin A., Vinet A. Effects of exercise training on arterial function in type 2 diabetes mellitus: a systematic review and meta-analysis. Sports Med. 2013;43:1191–1199.
    1. Okada S., Hiuge A., Makino H., Nagumo A., Takaki H., Konishi H. Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes. J Atheroscler Thromb. 2010;17:828–833.
    1. Kaiser N., Sasson S., Feener E.P., Boukobza-Vardi N., Higashi S., Moller D.E. Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes. 1993;42:80–89.
    1. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54:1615–1625.
    1. Giacco F., Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107:1058–1070.
    1. Vikramadithyan R.K., Hu Y., Noh H.L., Liang C.P., Hallam K., Tall A.R. Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. J Clin Invest. 2005;115:2434–2443.
    1. Yao D., Brownlee M. Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes. 2010;59:249–255.
    1. Goldin A., Beckman J.A., Schmidt A.M., Creager M.A. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605.
    1. Geraldes P., King G.L. Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res. 2010;106:1319–1331.
    1. Pieper G.M., Riaz ul H. Activation of nuclear factor-kappaB in cultured endothelial cells by increased glucose concentration: prevention by calphostin C. J Cardiovasc Pharmacol. 1997;30:528–532.
    1. Williams B., Gallacher B., Patel H., Orme C. Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes. 1997;46:1497–1503.
    1. Du X.L., Edelstein D., Rossetti L., Fantus I.G., Goldberg H., Ziyadeh F. Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Nat Acad Sci U S A. 2000;97:12222–12226.
    1. Kolm-Litty V., Sauer U., Nerlich A., Lehmann R., Schleicher E.D. High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest. 1998;101:160–169.
    1. Sayeski P.P., Kudlow J.E. Glucose metabolism to glucosamine is necessary for glucose stimulation of transforming growth factor-alpha gene transcription. J Biol Chem. 1996;271:15237–15243.
    1. Pierce G.L., Lesniewski L.A., Lawson B.R., Beske S.D., Seals D.R. Nuclear factor-{kappa}B activation contributes to vascular endothelial dysfunction via oxidative stress in overweight/obese middle-aged and older humans. Circulation. 2009;119:1284–1292.
    1. Manrique C., Lastra G., Sowers J.R. New insights into insulin action and resistance in the vasculature. Ann N Y Acad Sci. 2014;1311:138–150.
    1. Colberg S.R., Sigal R.J., Fernhall B., Regensteiner J.G., Blissmer B.J., Rubin R.R. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement executive summary. Diabetes Care. 2010;33:2692–2696.
    1. Albright A., Franz M., Hornsby G., Kriska A., Marrero D., Ullrich I. American College of Sports Medicine position stand. Exercise and type 2 diabetes. Med Sci Sports Exerc. 2000;32:1345–1360.
    1. De Filippis E., Cusi K., Ocampo G., Berria R., Buck S., Consoli A. Exercise-induced improvement in vasodilatory function accompanies increased insulin sensitivity in obesity and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2006;91:4903–4910.
    1. Maiorana A., O’Driscoll G., Cheetham C., Dembo L., Stanton K., Goodman C. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. J Am Coll Cardiol. 2001;38:860–866.
    1. Mitranun W., Deerochanawong C., Tanaka H., Suksom D. Continuous vs interval training on glycemic control and macro- and microvascular reactivity in type 2 diabetic patients. Scand J Med Sci Sports. 2014;24:e69–e76.
    1. Miche E., Herrmann G., Nowak M., Wirtz U., Tietz M., Hurst M. Effect of an exercise training program on endothelial dysfunction in diabetic and non-diabetic patients with severe chronic heart failure. Clin Res Cardiol. 2006;95(Suppl 1):i117–i124.
    1. Middlebrooke A.R., Elston L.M., Macleod K.M., Mawson D.M., Ball C.I., Shore A.C. Six months of aerobic exercise does not improve microvascular function in type 2 diabetes mellitus. Diabetologia. 2006;49:2263–2271.
    1. Schreuder T.H., Duncker D.J., Hopman M.T., Thijssen D.H. Randomized controlled trial using bosentan to enhance the impact of exercise training in subjects with type 2 diabetes mellitus. Exptl Physiol. 2014;99:1538–1547.
    1. Lavrencic A., Salobir B.G., Keber I. Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome. Arterioscler Thromb Vasc Biol. 2000;20:551–555.
    1. Vinet A., Obert P., Dutheil F., Diagne L., Chapier R., Lesourd B. Impact of a lifestyle program on vascular insulin resistance in metabolic syndrome subjects: the RESOLVE study. J Clin Endocrinol Metab. 2015;100:442–450.
    1. Gomes V.A., Casella-Filho A., Chagas A.C., Tanus-Santos J.E. Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome. Nitric Oxide Biol. 2008;19:345–350.
    1. Quinteiro H., Buzin M., Conti F.F., Dias Dda S., Figueroa D., Liesuy S. Aerobic exercise training promotes additional cardiac benefits better than resistance exercise training in postmenopausal rats with diabetes. Menopause. 2015;22:534–541.
    1. Rigla M., Fontcuberta J., Mateo J., Caixas A., Pou J.M., de Levia A. Physical training decreases plasma thrombomodulin in type I and type II diabetic patients. Diabetologia. 2001;44:693–699.
    1. Zoppini G., Targher G., Zamboni C., Venturi C., Cacciatori V., Moghetti P. Effects of moderate-intensity exercise training on plasma biomarkers of inflammation and endothelial dysfunction in older patients with type 2 diabetes. Nutrit Metab Cardiovasc Dis. 2006;16:543–549.
    1. Park Y., Booth F.W., Lee S., Laye M.J., Zhang C. Physical activity opposes coronary vascular dysfunction induced during high fat feeding in mice. J Physiol. 2012;590:4255–4268.
    1. Lamping K.G., Nuno D.W., Coppey L.J., Holmes A.J., Hu S., Oltman C.L. Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction. Diabetes Obesity Metab. 2013;15:144–152.
    1. DeMarco V.G., Habibi J., Jia G., Aroor A.R., Ramirez-Perez F.I., Martinez-Lemus L.A. Low-dose mineralocorticoid receptor blockade prevents western diet-induced arterial stiffening in female mice. Hypertension. 2015;66:99–107.
    1. Xu X., Ying Z., Cai M., Xu Z., Li Y., Jiang S.Y. Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue. Am J Physiol Regulat Integrat Compar Physiol. 2011;300:R1115–R1125.
    1. Jang H.J., Ridgeway S.D., Kim J.A. Effects of the green tea polyphenol epigallocatechin-3-gallate on high-fat diet-induced insulin resistance and endothelial dysfunction. Am J Physiol Endocrinol Metab. 2013;305:E1444–E1451.
    1. Lee S., Zhang H., Chen J., Dellsperger K.C., Hill M.A., Zhang C. Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice. Am J Physiol Heart Circ Physiol. 2012;303:H106–H115.
    1. Kim J.A., Jang H.J., Hwang D.H. Toll-like receptor 4-induced endoplasmic reticulum stress contributes to impairment of vasodilator action of insulin. Am J Physiol Endocrinol Metab. 2015;309:E767–E776.
    1. Bender S.B., Castorena-Gonzalez J.A., Garro M., Reyes-Aldasoro C.C., Sowers J.R., DeMarco V.G. Regional variation in arterial stiffening and dysfunction in Western diet-induced obesity. Am J Physiol Heart Circ Physiol. 2015;309:H574–H582.
    1. Toral M., Gomez-Guzman M., Jimenez R., Romero M., Zarzuelo M.J., Utrilla M.P. Chronic peroxisome proliferator-activated receptorbeta/delta agonist GW0742 prevents hypertension, vascular inflammatory and oxidative status, and endothelial dysfunction in diet-induced obesity. J Hypertens. 2015;33:1831–1844.
    1. Li Kwok Cheong J.D., Croft K.D., Henry P.D., Matthews V., Hodgson J.M., Ward N.C. Green coffee polyphenols do not attenuate features of the metabolic syndrome and improve endothelial function in mice fed a high fat diet. Arch Biochem Biophys. 2014;559:46–52.
    1. Aoqui C., Chmielewski S., Scherer E., Eissler R., Sollinger D., Heid I. Microvascular dysfunction in the course of metabolic syndrome induced by high-fat diet. Cardiovasc Diabetol. 2014;13:31.
    1. Zhang Q.J., Holland W.L., Wilson L., Tanner J.M., Keams D., Cahoon J.M. Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex. Diabetes. 2012;61:1848–1859.
    1. Donato A.J., Henson G.D., Hart C.R., Layec G., Trinity J.D., Bramwell R.C. The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction. J Physiol. 2014;592:4083–4096.
    1. Marchesi C., Ebrahimian T., Angulo O., Paradis P., Schiffrin E.L. Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension. 2009;54:1384–1392.
    1. Trask A.J., Katz P.S., Kelly A.P., Galantowicz M.L., Cismowski M.J., West T.A. Dynamic micro- and macrovascular remodeling in coronary circulation of obese Ossabaw pigs with metabolic syndrome. J Appl Physiol. 2012;113:1128–1140.
    1. Mikus C.R., Roseguini B.T., Uptergrove G.M., Morris E.M., Rector R.S., Libia J.L. Voluntary wheel running selectively augments insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats. Microcirculation. 2012;19:729–738.
    1. Bender S.B., Newcomer S.C., Harold Laughlin M. Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity. Am J Physiol Heart Circ Physiol. 2011;300:H1434–H1441.
    1. Haram P.M., Kemi O.J., Lee S.J., Bendheim M.O., Al-Share Q.Y., Waldum H.L. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovasc Res. 2009;81:723–732.

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