CoChat
Sign Up
Cited by 44Cardiovascular and exercise physiologyPhysical Activity and HealthDiabetes Management and Research

Mechanisms of aerobic exercise impairment in diabetes: a narrative review

Open access
Wahl, Matthew P., Scalzo, Rebecca L., Regensteiner, Judith G., Reusch, Jane E. B.·2018·Frontiers in Endocrinology
DOI 10.3389/fendo.2018.00181PMC PMC5915473
Open this paper in CoChat — free accountOpen PDF

Abstract

The prevalence of diabetes in the United States and globally has been rapidly increasing over the last several decades. There are now estimated to be 30.3 million people in the United States and 422 million people worldwide with diabetes. Diabetes is associated with a greatly increased risk of cardiovascular mortality, which is the leading cause of death in adults with diabetes. While exercise training is a cornerstone of diabetes treatment, people with diabetes have well-described aerobic exercise impairments that may create an additional diabetes-specific barrier to adding regular exercise to their lifestyle. Physiologic mechanisms linked to exercise impairment in diabetes include insulin resistance, cardiac abnormalities, mitochondrial function, and the ability of the body to supply oxygen. In this paper, we highlight the abnormalities of exercise in type 2 diabetes as well as potential therapeutic approaches.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fendo.2018.00181

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Many studies have reported that individuals with type 2 diabetes suffer from disease-related barriers to exercise adoption and diet modulation.

    “Further, many studies have reported that individuals withT2D suffer from disease‐related barriers to exercise adoption and diet modulation (Vijan 2005; Wahl 2018).”

    From Mindfulness-based interventions for adults with type 2 diabetes mellitus (2021) · cites this paper as Wahl 2018

    The Abstract and Clinical Impact sections describe diabetes-related exercise impairments that may make regular exercise harder for people with T2D. They do not describe disease-related barriers to diet modulation, so Wahl (2018) supports only the exercise portion of the claim. The supplied copy has no page numbers for these sections. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 125 · Cited by 44

Research works printed but not linked: 97

  1. [1]Cheng YJ Imperatore G Geiss LS Wang J Saydah SH Cowie CC Secular changes in the age-specific prevalence of diabetes among U.S. adults: 1988–2010. Diabetes Care (2013) 36(9): 2690– 6. 10.2337/dc12-2074 23637354 PMC3747941 · DOI
  2. [3]Haffner SM Lehto S Ronnemaa T Pyorala K Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med (1998) 339(4): 229– 34. 10.1056/NEJM199807233390404 9673301 · DOI · Paper page
  3. [5]Bommer C Heesemann E Sagalova V Manne-Goehler J Atun R Barnighausen T The global economic burden of diabetes in adults aged 20–79 years: a cost-of-illness study. Lancet Diabetes Endocrinol (2017) 5(6): 423– 30. 10.1016/S2213-8587(17)30097-9 28456416 · DOI
  4. [6]Bommer C Sagalova V Heesemann E Manne-Goehler J Atun R Barnighausen T Global economic burden of diabetes in adults: projections from 2015 to 2030. Diabetes Care (2018) 41(4): dc171962. 10.2337/dc17-1962 29475843 · DOI
  5. [11]Wei M Gibbons LW Kampert JB Nichaman MZ Blair SN. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med (2000) 132(8): 605– 11. 10.7326/0003-4819-132-8-200004180-00035 10766678 · DOI
  6. [12]Cooper AJ Brage S Ekelund U Wareham NJ Griffin SJ Simmons RK. Association between objectively assessed sedentary time and physical activity with metabolic risk factors among people with recently diagnosed type 2 diabetes. Diabetologia (2014) 57(1): 73– 82. 10.1007/s00125-013-3069-8 24196189 PMC3857880 · DOI
  7. [13]de Borba AT Jost RT Gass R Nedel FB Cardoso DM Pohl HH The influence of active and passive smoking on the cardiorespiratory fitness of adults. Multidiscip Respir Med (2014) 9(1): 34. 10.1186/2049-6958-9-34 25009739 PMC4088222 · DOI
  8. [14]Mondal H Mishra SP. Effect of BMI, body fat percentage and fat free mass on maximal oxygen consumption in healthy young adults. J Clin Diagn Res (2017) 11(6): CC17– 20. 10.7860/JCDR/2017/25465.10039 28764152 PMC5535345 · DOI
  9. [15]Dumuid D Lewis LK Olds TS Maher C Bondarenko C Norton L. Relationships between older adults’ use of time and cardio-respiratory fitness, obesity and cardio-metabolic risk: a compositional isotemporal substitution analysis. Maturitas (2018) 110: 104– 10. 10.1016/j.maturitas.2018.02.003 29563028 · DOI
  10. [16]Yoon JH So WY. Associations of hypertension status with physical fitness variables in Korean women. Iran J Public Health (2013) 42(7): 673– 80. 24427746 PMC3881613
  11. [17]Mazic S Suzic Lazic J Dekleva M Antic M Soldatovic I Djelic M The impact of elevated blood pressure on exercise capacity in elite athletes. Int J Cardiol (2015) 180: 171– 7. 10.1016/j.ijcard.2014.11.125 25460373 · DOI
  12. [18]Jae SY Kurl S Franklin BA Laukkanen JA. Changes in cardiorespiratory fitness predict incident hypertension: a population-based long-term study. Am J Hum Biol (2017) 29(3): e22932. 10.1002/ajhb.22932 27753165 · DOI
  13. [19]Regensteiner JG Bauer TA Reusch JE Quaife RA Chen MY Smith SC Cardiac dysfunction during exercise in uncomplicated type 2 diabetes. Med Sci Sports Exerc (2009) 41(5): 977– 84. 10.1249/MSS.0b013e3181942051 19346991 PMC2903427 · DOI
  14. [20]Regensteiner JG Sippel J McFarling ET Wolfel EE Hiatt WR. Effects of non-insulin-dependent diabetes on oxygen consumption during treadmill exercise. Med Sci Sports Exerc (1995) 27(6): 875– 81. 10.1249/00005768-199505000-00007 7658949 · DOI
  15. [21]Brandenburg SL Reusch JE Bauer TA Jeffers BW Hiatt WR Regensteiner JG. Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes. Diabetes Care (1999) 22(10): 1640– 6. 10.2337/diacare.22.10.1640 10526728 · DOI
  16. [22]Bauer TA Reusch JE Levi M Regensteiner JG Skeletal muscle deoxygenation following the onset of moderate exercise suggests slowed microvascular blood flow kinetics in type 2 diabetes. Diabetes Care (2007) 30(11): 2880– 5. 10.2337/dc07-0843 17675540 · DOI
  17. [23]Nadeau KJ Zeitler PS Bauer TA Brown MS Dorosz JL Draznin B Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J Clin Endocrinol Metab (2009) 94(10): 3687– 95. 10.1210/jc.2008-2844 19584191 PMC2758737 · DOI
  18. [24]Nadeau KJ Regensteiner JG Bauer TA Brown MS Dorosz JL Hull A Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab (2010) 95(2): 513– 21. 10.1210/jc.2009-1756 19915016 PMC2840859 · DOI
  19. [25]Ross R Blair SN Arena R Church TS Despres JP Franklin BA Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign: a scientific statement from the American Heart Association. Circulation (2016) 134(24): e653– 99. 10.1161/CIR.0000000000000461 27881567 · DOI · Paper page
  20. [26]Lee CD Blair SN Jackson AS. Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men. Am J Clin Nutr (1999) 69(3): 373– 80. 10.1093/ajcn/69.3.373 10075319 · DOI
  21. [27]Wei M Kampert JB Barlow CE Nichaman MZ Gibbons LW Paffenbarger RS Jr Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA (1999) 282(16): 1547– 53. 10.1001/jama.282.16.1547 10546694 · DOI · Paper page
  22. [29]Regensteiner JG Bauer TA Reusch JE Brandenburg SL Sippel JM Vogelsong AM Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus. J Appl Physiol (1985) (1998) 85(1): 310– 7. 10.1152/jappl.1998.85.1.310 9655791 · DOI
  23. [30]Huebschmann AG Reis EN Emsermann C Dickinson LM Reusch JE Bauer TA Women with type 2 diabetes perceive harder effort during exercise than nondiabetic women. Appl Physiol Nutr Metab (2009) 34(5): 851– 7. 10.1139/H09-074 19935846 · DOI
  24. [31]Regensteiner JG Bauer TA Reusch JE. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care (2005) 28(12): 2877– 83. 10.2337/diacare.28.12.2877 16306548 · DOI
  25. [32]Subudhi AW Dimmen AC Roach RC Effects of acute hypoxia on cerebral and muscle oxygenation during incremental exercise. J Appl Physiol (1985) (2007) 103(1): 177– 83. 10.1152/japplphysiol.01460.2006 17431082 · DOI
  26. [33]MacAnaney O Reilly H O’Shea D Egana M Green S. Effect of type 2 diabetes on the dynamic response characteristics of leg vascular conductance during exercise. Diab Vasc Dis Res (2011) 8(1): 12– 21. 10.1177/1479164110389625 21262866 · DOI
  27. [34]Jones WS Duscha BD Robbins JL Duggan NN Regensteiner JG Kraus WE Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training. Vasc Med (2012) 17(2): 94– 100. 10.1177/1358863X11436334 22402934 PMC3609421 · DOI
  28. [35]Macananey O O’Shea D Warmington SA Green S Egana M. Gymnasium-based unsupervised exercise maintains benefits in oxygen uptake kinetics obtained following supervised training in type 2 diabetes. Appl Physiol Nutr Metab (2012) 37(4): 599– 609. 10.1139/h2012-012 22563745 · DOI
  29. [36]Huebschmann AG Kohrt WM Herlache L Wolfe P Daugherty S Reusch JE Type 2 diabetes exaggerates exercise effort and impairs exercise performance in older women. BMJ Open Diabetes Res Care (2015) 3(1): e000124. 10.1136/bmjdrc-2015-000124 26464803 PMC4597414 · DOI
  30. [37]Schneider SH Amorosa LF Khachadurian AK Ruderman NB. Studies on the mechanism of improved glucose control during regular exercise in type 2 (non-insulin-dependent) diabetes. Diabetologia (1984) 26(5): 355– 60. 10.1007/BF00266036 6376244 · DOI
  31. [38]Kjaer M Hollenbeck CB Frey-Hewitt B Galbo H Haskell W Reaven GM. Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes. J Appl Physiol (1985) (1990) 68(5): 2067– 74. 10.1152/jappl.1990.68.5.2067 2193907 · DOI · Paper page
  32. [39]Mac Ananey O Malone J Warmington S O’Shea D Green S Egana M. Cardiac output is not related to the slowed O2 uptake kinetics in type 2 diabetes. Med Sci Sports Exerc (2011) 43(6): 935– 42. 10.1249/MSS.0b013e3182061cdb 21131874 · DOI
  33. [40]Gusso S Hofman P Lalande S Cutfield W Robinson E Baldi JC. Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus. Diabetologia (2008) 51(7): 1317– 20. 10.1007/s00125-008-1012-1 18446317 · DOI · Paper page
  34. [41]Wilkerson DP Poole DC Jones AM Fulford J Mawson DM Ball CI Older type 2 diabetic males do not exhibit abnormal pulmonary oxygen uptake and muscle oxygen utilization dynamics during submaximal cycling exercise. Am J Physiol Regul Integr Comp Physiol (2011) 300(3): R685– 92. 10.1152/ajpregu.00479.2010 21178129 · DOI
  35. [42]Hamman RF Wing RR Edelstein SL Lachin JM Bray GA Delahanty L Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care (2006) 29(9): 2102– 7. 10.2337/dc06-0560 16936160 PMC1762038 · DOI · Paper page
  36. [44]Morss GM Jordan AN Skinner JS Dunn AL Church TS Earnest CP Dose response to exercise in women aged 45–75 yr (DREW): design and rationale. Med Sci Sports Exerc (2004) 36(2): 336– 44. 10.1249/01.MSS.0000113738.06267.E5 14767260 · DOI
  37. [45]Slentz CA Aiken LB Houmard JA Bales CW Johnson JL Tanner CJ Inactivity, exercise, and visceral fat. STRRIDE: a randomized, controlled study of exercise intensity and amount. J Appl Physiol (1985) (2005) 99(4): 1613– 8. 10.1152/japplphysiol.00124.2005 16002776 · DOI · Paper page
  38. [46]Thompson AM Mikus CR Rodarte RQ Distefano B Priest EL Sinclair E Inflammation and exercise (INFLAME): study rationale, design, and methods. Contemp Clin Trials (2008) 29(3): 418– 27. 10.1016/j.cct.2007.09.009 18024231 PMC2435622 · DOI
  39. [48]Regensteiner JG Bauer TA Huebschmann AG Herlache L Weinberger HD Wolfel EE Sex differences in the effects of type 2 diabetes on exercise performance. Med Sci Sports Exerc (2015) 47(1): 58– 65. 10.1249/MSS.0000000000000371 24811327 PMC4296732 · DOI
  40. [49]Ring M Eriksson MJ Fritz T Nyberg G Ostenson CG Krook A Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance. Diab Vasc Dis Res (2015) 12(5): 315– 24. 10.1177/1479164115588548 26092821 PMC4527971 · DOI
  41. [52]Kadoglou NP Iliadis F Sailer N Athanasiadou Z Vitta I Kapelouzou A Exercise training ameliorates the effects of rosiglitazone on traditional and novel cardiovascular risk factors in patients with type 2 diabetes mellitus. Metabolism (2010) 59(4): 599– 607. 10.1016/j.metabol.2009.09.002 19922961 · DOI
  42. [53]Kim JC The effect of exercise training combined with PPARgamma agonist on skeletal muscle glucose uptake and insulin sensitivity in induced diabetic obese Zucker rats. J Exerc Nutrition Biochem (2016) 20(2): 42– 50. 10.20463/jenb.2016.06.20.2.6 PMC4977909 27508153 · DOI
  43. [56]Braun B Eze P Stephens BR Hagobian TA Sharoff CG Chipkin SR Impact of metformin on peak aerobic capacity. Appl Physiol Nutr Metab (2008) 33(1): 61– 7. 10.1139/H07-144 18347654 · DOI
  44. [57]Cadeddu C Nocco S Deidda M Cadeddu F Bina A Demuru P Cardiopulmonary and endothelial effects of metformin treatment in an insulin resistant population. Int J Cardiol (2012) 158(2): 302– 4. 10.1016/j.ijcard.2012.04.113 22622058 · DOI
  45. [58]Paul AA Dkhar SA Kamalanathan S Thabah MM George M Chandrasekaran I Effect of metformin on exercise capacity in metabolic syndrome. Diabetes Metab Syndr (2017) 11(Suppl 1): S403– 6. 10.1016/j.dsx.2017.03.025 28283393 · DOI
  46. [59]Malin SK Gerber R Chipkin SR Braun B. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care (2012) 35(1): 131– 6. 10.2337/dc11-0925 22040838 PMC3241331 · DOI
  47. [61]Leverve XM Guigas B Detaille D Batandier C Koceir EA Chauvin C Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab (2003) 29(4 Pt 2): S88– 94. 10.1016/S1262-3636(03)72792-X 14502105 · DOI
  48. [62]Batandier C Guigas B Detaille D El-Mir MY Fontaine E Rigoulet M The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin. J Bioenerg Biomembr (2006) 38(1): 33– 42. 10.1007/s10863-006-9003-8 16732470 · DOI
  49. [65]Sparks LM. Exercise training response heterogeneity: physiological and molecular insights. Diabetologia (2017) 60(12): 2329– 36. 10.1007/s00125-017-4461-6 29032385 · DOI · Paper page
  50. [66]Kelley DE He J Menshikova EV Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes (2002) 51(10): 2944– 50. 10.2337/diabetes.51.10.2944 12351431 · DOI · Paper page
  51. [67]Bugger H Abel ED. Mitochondria in the diabetic heart. Cardiovasc Res (2010) 88(2): 229– 40. 10.1093/cvr/cvq239 20639213 PMC2952534 · DOI
  52. [68]Knaub LA McCune S Chicco AJ Miller M Moore RL Birdsey N Impaired response to exercise intervention in the vasculature in metabolic syndrome. Diab Vasc Dis Res (2013) 10(3): 222– 38. 10.1177/1479164112459664 23162060 PMC4139293 · DOI
  53. [69]Davidson SM Endothelial mitochondria and heart disease. Cardiovasc Res (2010) 88(1): 58– 66. 10.1093/cvr/cvq195 20558442 · DOI
  54. [70]Keller AC Knaub LA Miller MW Birdsey N Klemm DJ Reusch JE. Saxagliptin restores vascular mitochondrial exercise response in the Goto-Kakizaki rat. J Cardiovasc Pharmacol (2015) 65(2): 137– 47. 10.1097/FJC.0000000000000170 25264749 PMC4320657 · DOI
  55. [71]Keller AC Knaub LA McClatchey PM Connon CA Bouchard R Miller MW Differential mitochondrial adaptation in primary vascular smooth muscle cells from a diabetic rat model. Oxid Med Cell Longev (2016) 2016: 8524267. 10.1155/2016/8524267 27034743 PMC4737048 · DOI
  56. [72]Brierley EJ Johnson MA James OF Turnbull DM. Effects of physical activity and age on mitochondrial function. QJM (1996) 89(4): 251– 8. 10.1093/qjmed/89.4.251 8733511 · DOI
  57. [73]Spina RJ Chi MM Hopkins MG Nemeth PM Lowry OH Holloszy JO. Mitochondrial enzymes increase in muscle in response to 7–10 days of cycle exercise. J Appl Physiol (1985) (1996) 80(6): 2250– 4. 10.1152/jappl.1996.80.6.2250 8806937 · DOI
  58. [74]Starritt EC Angus D Hargreaves M Effect of short-term training on mitochondrial ATP production rate in human skeletal muscle. J Appl Physiol (1985) (1999) 86(2): 450– 4. 10.1152/jappl.1999.86.2.450 9931175 · DOI
  59. [75]Ji LL. Exercise-induced modulation of antioxidant defense. Ann N Y Acad Sci (2002) 959: 82– 92. 10.1111/j.1749-6632.2002.tb02085.x 11976188 · DOI
  60. [76]Young CG Knight CA Vickers KC Westbrook D Madamanchi NR Runge MS Differential effects of exercise on aortic mitochondria. Am J Physiol Heart Circ Physiol (2005) 288(4): H1683– 9. 10.1152/ajpheart.00136.2004 15550530 · DOI
  61. [77]Montagnani M Chen H Barr VA Quon MJ. Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem (2001) 276(32): 30392– 8. 10.1074/jbc.M103702200 11402048 · DOI
  62. [78]Nisoli E Clementi E Paolucci C Cozzi V Tonello C Sciorati C Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science (2003) 299(5608): 896– 9. 10.1126/science.1079368 12574632 · DOI · Paper page
  63. [79]Miller MW Knaub LA Olivera-Fragoso LF Keller AC Balasubramaniam V Watson PA Nitric oxide regulates vascular adaptive mitochondrial dynamics. Am J Physiol Heart Circ Physiol (2013) 304(12): H1624– 33. 10.1152/ajpheart.00987.2012 23585138 PMC3680775 · DOI
  64. [80]Krotkiewski M Lonnroth P Mandroukas K Wroblewski Z Rebuffe-Scrive M Holm G The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia (1985) 28(12): 881– 90. 10.1007/BF00703130 3912243 · DOI
  65. [81]Kirwan JP Kohrt WM Wojta DM Bourey RE Holloszy JO. Endurance exercise training reduces glucose-stimulated insulin levels in 60- to 70-year-old men and women. J Gerontol (1993) 48(3): M84– 90. 10.1093/geronj/48.3.M84 8482816 · DOI
  66. [82]Marliss EB Vranic M. Intense exercise has unique effects on both insulin release and its roles in glucoregulation: implications for diabetes. Diabetes (2002) 51(Suppl 1): S271– 83. 10.2337/diabetes.51.2007.S271 11815492 · DOI · Paper page
  67. [83]Kiraly MA Bates HE Kaniuk NA Yue JT Brumell JH Matthews SG Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of beta-cell function. Am J Physiol Endocrinol Metab (2008) 294(2): E271– 83. 10.1152/ajpendo.00476.2007 18029442 · DOI
  68. [84]Park S Hong SM Sung SR. Exendin-4 and exercise promotes beta-cell function and mass through IRS2 induction in islets of diabetic rats. Life Sci (2008) 82(9–10): 503– 11. 10.1016/j.lfs.2007.12.018 18237751 · DOI
  69. [86]Fink RI Kolterman OG Griffin J Olefsky JM Mechanisms of insulin resistance in aging. J Clin Invest (1983) 71(6): 1523– 35. 10.1172/JCI110908 6345584 PMC370358 · DOI
  70. [87]Iozzo P Beck-Nielsen H Laakso M Smith U Yki-Jarvinen H Ferrannini E. Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab (1999) 84(3): 863– 8. 10.1210/jcem.84.3.5542 10084562 · DOI
  71. [88]Szoke E Shrayyef MZ Messing S Woerle HJ van Haeften TW Meyer C Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell function in individuals with impaired glucose tolerance. Diabetes Care (2008) 31(3): 539– 43. 10.2337/dc07-1443 18083793 · DOI
  72. [89]De Tata V. Age-related impairment of pancreatic beta-cell function: pathophysiological and cellular mechanisms. Front Endocrinol (2014) 5: 138. 10.3389/fendo.2014.00138 25232350 PMC4153315 · DOI
  73. [90]Santulli G Lombardi A Sorriento D Anastasio A Del Giudice C Formisano P Age-related impairment in insulin release: the essential role of beta(2)-adrenergic receptor. Diabetes (2012) 61(3): 692– 701. 10.2337/db11-1027 22315324 PMC3282797 · DOI
  74. [91]Lin Y Sun Z Antiaging gene Klotho enhances glucose-induced insulin secretion by up-regulating plasma membrane levels of TRPV2 in MIN6 beta-cells. Endocrinology (2012) 153(7): 3029– 39. 10.1210/en.2012-1091 22597535 PMC3380305 · DOI
  75. [93]Rogers MA Hagberg JM Martin WH III Ehsani AA Holloszy JO. Decline in VO2max with aging in master athletes and sedentary men. J Appl Physiol (1985) (1990) 68(5): 2195– 9. 10.1152/jappl.1990.68.5.2195 2361923 · DOI
  76. [94]Ishihara H Maechler P Gjinovci A Herrera PL Wollheim CB. Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat Cell Biol (2003) 5(4): 330– 5. 10.1038/ncb951 12640462 · DOI
  77. [96]Lu H Koshkin V Allister EM Gyulkhandanyan AV Wheeler MB. Molecular and metabolic evidence for mitochondrial defects associated with beta-cell dysfunction in a mouse model of type 2 diabetes. Diabetes (2010) 59(2): 448– 59. 10.2337/db09-0129 19903739 PMC2809957 · DOI
  78. [97]Lombardi A Trimarco B Iaccarino G Santulli G. Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure. Cell Commun Signal (2017) 15(1): 47. 10.1186/s12964-017-0203-0 29132395 PMC5684747 · DOI
  79. [98]Gros R You X Baggio LL Kabir MG Sadi AM Mungrue IN Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology (2003) 144(6): 2242– 52. 10.1210/en.2003-0007 12746281 · DOI
  80. [100]Chai W Dong Z Wang N Wang W Tao L Cao W Glucagon-like peptide 1 recruits microvasculature and increases glucose use in muscle via a nitric oxide-dependent mechanism. Diabetes (2012) 61(4): 888– 96. 10.2337/db11-1073 22357961 PMC3314347 · DOI · Paper page
  81. [101]Dong Z Chai W Wang W Zhao L Fu Z Cao W Protein kinase A mediates glucagon-like peptide 1-induced nitric oxide production and muscle microvascular recruitment. Am J Physiol Endocrinol Metab (2013) 304(2): E222– 8. 10.1152/ajpendo.00473.2012 23193054 PMC3543568 · DOI
  82. [102]Scalzo RL Moreau KL Ozemek C Herlache L McMillin S Gilligan S Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes. J Diabetes Complications (2017) 31(2): 449– 55. 10.1016/j.jdiacomp.2016.10.003 27884660 PMC5787373 · DOI
  83. [104]Fan W Waizenegger W Lin CS Sorrentino V He MX Wall CE PPARdelta promotes running endurance by preserving glucose. Cell Metab (2017) 25(5): 1186– 93.e4. 10.1016/j.cmet.2017.04.006 28467934 PMC5492977 · DOI · Paper page
  84. [106]Neal B Perkovic V Mahaffey KW de Zeeuw D Fulcher G Erondu N Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med (2017) 377(7): 644– 57. 10.1056/NEJMoa1611925 28605608 · DOI · Paper page
  85. [107]O’Brien TP Jenkins EC Estes SK Castaneda AV Ueta K Farmer TD Correcting postprandial hyperglycemia in Zucker diabetic fatty rats with an SGLT2 inhibitor restores glucose effectiveness in the liver and reduces insulin resistance in skeletal muscle. Diabetes (2017) 66(5): 1172– 84. 10.2337/db16-1410 28246292 PMC5399614 · DOI
  86. [108]Diaz-Rodriguez E Agra RM Fernandez AL Adrio B Garcia-Caballero T Gonzalez-Juanatey JR Effects of dapagliflozin on human epicardial adipose tissue: modulation of insulin resistance, inflammatory chemokine production, and differentiation ability. Cardiovasc Res (2018) 114(2): 336– 46. 10.1093/cvr/cvx186 29016744 · DOI
  87. [109]Li CY Wang LX Dong SS Hong Y Zhou XH Zheng WW Phlorizin exerts direct protective effects on palmitic acid (PA)-induced endothelial dysfunction by activating the PI3K/AKT/eNOS signaling pathway and increasing the levels of nitric oxide (NO). Med Sci Monit Basic Res (2018) 24: 1– 9. 10.12659/MSMBR.907775 29307883 PMC5771185 · DOI
  88. [110]Radholm K Figtree G Perkovic V Solomon SD Mahaffey KW de Zeeuw D Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS program (Canagliflozin Cardiovascular Assessment Study). Circulation (2018). 10.1161/CIRCULATIONAHA.118.034222 PMC6075881 29526832 · DOI · Paper page
  89. [112]Chilton R Tikkanen I Cannon CP Crowe S Woerle HJ Broedl UC Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab (2015) 17(12): 1180– 93. 10.1111/dom.12572 26343814 PMC5057299 · DOI · Paper page
  90. [113]Fioretto P Zambon A Rossato M Busetto L Vettor R. SGLT2 inhibitors and the diabetic kidney. Diabetes Care (2016) 39(Suppl 2): S165– 71. 10.2337/dcS15-3006 27440829 · DOI
  91. [114]Wanner C Inzucchi SE Lachin JM Fitchett D von Eynatten M Mattheus M Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med (2016) 375(4): 323– 34. 10.1056/NEJMoa1515920 27299675 · DOI · Paper page
  92. [115]Habibi J Aroor AR Sowers JR Jia G Hayden MR Garro M Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc Diabetol (2017) 16(1): 9. 10.1186/s12933-016-0489-z 28086951 PMC5237274 · DOI
  93. [116]Packer M Anker SD Butler J Filippatos G Zannad F. Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol (2017) 2(9): 1025– 9. 10.1001/jamacardio.2017.2275 28768320 · DOI
  94. [117]Wadley GD Choate J McConell GK NOS isoform-specific regulation of basal but not exercise-induced mitochondrial biogenesis in mouse skeletal muscle. J Physiol (2007) 585(Pt 1): 253– 62. 10.1113/jphysiol.2007.141309 17916611 PMC2375470 · DOI
  95. [121]Mason McClatchey P Bauer TA Regensteiner JG Schauer IE Huebschmann AG Reusch JEB. Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes. J Diabetes Complications (2017) 31(8): 1311– 7. 10.1016/j.jdiacomp.2017.05.004 28571935 PMC5891220 · DOI
  96. [122]McClatchey PM Frisbee JC Reusch JEB. A conceptual framework for predicting and addressing the consequences of disease-related microvascular dysfunction. Microcirculation (2017) 24(6): e12359. 10.1111/micc.12359 28135021 PMC6258047 · DOI
  97. [123]Mason McClatchey P Wu F Olfert IM Ellis CG Goldman D Reusch JE Impaired tissue oxygenation in metabolic syndrome requires increased microvascular perfusion heterogeneity. J Cardiovasc Transl Res (2017) 10(1): 69– 81. 10.1007/s12265-017-9732-6 28168652 PMC5893163 · DOI

Authors
Wahl, M. P., Scalzo, R. L., Regensteiner, J. G., & Reusch, J. E. B.
Affiliations
  • VA Eastern Colorado Health Care System (US)
  • University of Colorado Anschutz (US)
Corresponding author
Reusch, Jane E. B.
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2018-04-18
Volume
9
Pages
181-181
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2018.00181
PMC
PMC5915473
OpenAlex
W2801490718
Cited by
44
References
125
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 12 · 2019: 6 · 2014: 1
FWCI
1.29
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Veterans Affairs (I01 CX001532, I01 BX002046)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (T32HL007171)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK048520)
  • National Center for Research Resources (UL1RR025780)
  • Colorado Clinical and Translational Sciences Institute (UL1-RR025780)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 2 diabetes, exercise capacity, insulin resistance, cardiac anomalies, mitochondrial function, oxygen supply, cardiovascular mortality, exercise training, treatment options

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review