Macro- and microvascular endothelial dysfunction in diabetes

Journal of Diabetes

Volumn 9, Issue 5, 2017, Pages 434-449

  Shi, Yi ^a   Vanhoutte, Paul M ^b  

^a FUDAN UNIVERSITY   (China)

^b UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

diabetes; endothelial cells; microvasculature; miRNA; nitric oxide

Indexed keywords

ANTIDIABETIC AGENT; ENDOTHELIN 1; MICRORNA; NITRIC OXIDE; PROSTACYCLIN; VASCULOTROPIN;

DIABETIC MICROANGIOPATHY; EDITORIAL; ENDOTHELIAL DYSFUNCTION; ENDOTHELIAL PROGENITOR CELL; EPIGENETICS; GLYCEMIC CONTROL; HUMAN; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; METABOLIC MEMORY; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; TISSUE REPAIR; VASOMOTOR REFLEX; ANIMAL; BLOOD VESSEL; DIABETES MELLITUS; DIABETIC ANGIOPATHY; GENETICS; MICROVASCULATURE; PATHOPHYSIOLOGY; VASCULAR ENDOTHELIUM;

ANIMALS; BLOOD VESSELS; DIABETES MELLITUS; DIABETIC ANGIOPATHIES; ENDOTHELIUM, VASCULAR; HUMANS; MICRORNAS; MICROVESSELS; NITRIC OXIDE; OXIDATIVE STRESS;

EID: 85014010148     PISSN: 17530393     EISSN: 17530407     Source Type: Journal    
DOI: 10.1111/1753-0407.12521     Document Type: Editorial

References (213)

1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288: 373–376.
2. Vanhoutte PM, Zhao Y, Xu A, Leung SW. Thirty years of saying no: Sources, fate, actions, and misfortunes of the endothelium-derived vasodilator mediator. Circ Res. 2016; 119: 375–396.
3. Vanhoutte PM, Shimokawa H, Feletou M, Tang EH. Endothelial dysfunction and vascular disease: A thirtieth anniversary update. Acta Physiol (Oxf). 2017; 219: 22–96.
4. Vanhoutte PM. How we learned to say no. Arterioscler Thromb Vasc Biol. 2009; 29: 1156–1160.
5. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27: 1047–1053.
6. Gilbert RE. Endothelial loss and repair in the vascular complications of diabetes: Pathogenetic mechanisms and therapeutic implications. Circ J. 2013; 77: 849–856.
7. Beermann J, Piccoli MT, Viereck J, Thum T. Non-coding RNAs in development and disease: Background, mechanisms, and therapeutic approaches. Physiol Rev. 2016; 96: 1297–1325.
8. Vienberg S, Geiger J, Madsen S, Dalgaard LT. MicroRNAs in metabolism. Acta Physiol (Oxf). 2017; 219: 346–361.
9. Shimokawa H, Yasutake H, Fujii K et al. The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol. 1996; 28: 703–711.
10. Feletou M, Vanhoutte PM. EDHF: An update. Clin Sci (Lond). 2009; 117: 139–155.
11. Zhou MS, Nishida Y, Chen QH, Kosaka H. Endothelium-derived contracting factor in carotid artery of hypertensive Dahl rats. Hypertension. 1999; 34: 39–43.
12. Vanhoutte PM, Tang EH. Endothelium-dependent contractions: When a good guy turns bad! J Physiol. 2008; 586: 5295–5304.
13. Wakabayashi I, Hatake K, Kimura N, Kakishita E, Nagai K. Modulation of vascular tonus by the endothelium in experimental diabetes. Life Sci. 1987; 40: 643–648.
14. Shi Y, Ku DD, Man RY, Vanhoutte PM. Augmented endothelium-derived hyperpolarizing factor-mediated relaxations attenuate endothelial dysfunction in femoral and mesenteric, but not in carotid arteries from type I diabetic rats. J Pharmacol Exp Ther. 2006; 318: 276–281.
15. De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM. Endothelial dysfunction in diabetes. Br J Pharmacol. 2000; 130: 963–974.
16. Shi Y, Vanhoutte PM. Reactive oxygen-derived free radicals are key to the endothelial dysfunction of diabetes. J Diabetes. 2009; 1: 151–162.
17. Paneni F, Costantino S, Castello L et al. Targeting prolyl-isomerase pin1 prevents mitochondrial oxidative stress and vascular dysfunction: Insights in patients with diabetes. Eur Heart J. 2015; 36: 817–828.
18. Matsumoto S, Shimabukuro M, Fukuda D et al. Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser(1177)/Thr(497) of endothelial nitric oxide synthase in diabetic mice. Cardiovasc Diabetol. 2014; 13: 30.
19. Yao L, Chandra S, Toque HA et al. Prevention of diabetes-induced arginase activation and vascular dysfunction by rho kinase (Rock) knockout. Cardiovasc Res. 2013; 97: 509–519.
20. Pernow J, Jung C. The emerging role of arginase in endothelial dysfunction in diabetes. Curr Vasc Pharmacol. 2016; 14: 155–162.
21. Bouras G, Deftereos S, Tousoulis D et al. Asymmetric dimethylarginine (ADMA): A promising biomarker for cardiovascular disease? Curr Top Med Chem. 2013; 13: 180–200.
22. Konstantinidis G, Head GA, Evans RG et al. Endothelial cationic amino acid transporter-1 overexpression can prevent oxidative stress and increases in arterial pressure in response to superoxide dismutase inhibition in mice. Acta Physiol (Oxf). 2014; 210: 845–853.
23. Kikuchi C, Kajikuri J, Hori E et al. Aortic superoxide production at the early hyperglycemic stage in a rat type 2 diabetes model and the effects of pravastatin. Biol Pharm Bull. 2014; 37: 996–1002.
24. Alves-Lopes R, Neves KB, Montezano AC et al. Internal pudental artery dysfunction in diabetes mellitus is mediated by NOX1-derived ROS-, Nrf2-, and Rho kinase-dependent mechanisms. Hypertension. 2016; 68: 1056–1064.
25. Feletou M, Tang EH, Vanhoutte PM. Nitric oxide the gatekeeper of endothelial vasomotor control. Front Biosci. 2008; 13: 4198–4217.
26. Gebremedhin D, Koltai MZ, Pogatsa G, Magyar K, Hadhazy P. Influence of experimental diabetes on the mechanical responses of canine coronary arteries: Role of endothelium. Cardiovasc Res. 1988; 22: 537–544.
27. Shen B, Ye CL, Ye KH, Liu JJ. Mechanism underlying enhanced endothelium-dependent vasodilatation in thoracic aorta of early stage streptozotocin-induced diabetic mice. Acta Pharmacol Sin. 2003; 24: 422–428.
28. 2 analogue. J Endocrinol. 2002; 175: 217–223.
29. Makino A, Ohuchi K, Kamata K. Mechanisms underlying the attenuation of endothelium-dependent vasodilatation in the mesenteric arterial bed of the streptozotocin-induced diabetic rat. Br J Pharmacol. 2000; 130: 549–556.
30. Matsumoto T, Kobayashi T, Kamata K. Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular contractions in the Otsuka Long-Evans Tokushima fatty (OLETF) rat aorta. Br J Pharmacol. 2006; 149: 931–941.
31. Triggle CR, Ding H, Anderson TJ, Pannirselvam M. The endothelium in health and disease: A discussion of the contribution of non-nitric oxide endothelium-derived vasoactive mediators to vascular homeostasis in normal vessels and in type II diabetes. Mol Cell Biochem. 2004; 263: 21–27.
32. Feletou M, Huang Y, Vanhoutte PM. Endothelium-mediated control of vascular tone: Cox-1 and cox-2 products. Br J Pharmacol. 2011; 164: 894–912.
33. Wong MS, Vanhoutte PM. Cox-mediated endothelium-dependent contractions: From the past to recent discoveries. Acta Pharmacol Sin. 2010; 31: 1095–1102.
34. Baretella O, Vanhoutte PM. Endothelium-dependent contractions: Prostacyclin and endothelin-1, partners in crime? Adv Pharmacol. 2016; 77: 177–208.
35. Shi Y, So KF, Man RY, Vanhoutte PM. Oxygen-derived free radicals mediate endothelium-dependent contractions in femoral arteries of rats with streptozotocin-induced diabetes. Br J Pharmacol. 2007; 152: 1033–1041.
36. Auch-Schwelk W, Katusic ZS, Vanhoutte PM. Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta. Hypertension. 1992; 19: 442–445.
37. Kassan M, Choi SK, Galan M, Trebak M, Belmadani S, Matrougui K. Nuclear factor kappa B inhibition improves conductance artery function in type 2 diabetic mice. Diabetes Metab Res Rev. 2015; 31: 39–49.
38. Ling X, Cota-Gomez A, Flores NC et al. Alterations in redox homeostasis and prostaglandins impair endothelial-dependent vasodilation in euglycemic autoimmune nonobese diabetic mice. Free Radic Biol Med. 2005; 39: 1089–1098.
39. Kagota S, Yamaguchi Y, Nakamura K, Kunitomo M. Altered endothelium-dependent responsiveness in the aortas and renal arteries of Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus. Gen Pharmacol. 2000; 34: 201–209.
40. Shi Y, Feletou M, Ku DD, Man RY, Vanhoutte PM. The calcium ionophore A23187 induces endothelium-dependent contractions in femoral arteries from rats with streptozotocin-induced diabetes. Br J Pharmacol. 2007; 150: 624–632.
41. Okon EB, Szado T, Laher I, McManus B, van Breemen C. Augmented contractile response of vascular smooth muscle in a diabetic mouse model. J Vasc Res. 2003; 40: 520–530.
42. Ramos-Alves FE, de Queiroz DB, Santos-Rocha J, Duarte GP, Xavier FE. Effect of age and cox-2-derived prostanoids on the progression of adult vascular dysfunction in the offspring of diabetic rats. Br J Pharmacol. 2012; 166: 2198–2208.
43. Vessieres E, Guihot AL, Toutain B et al. Cox-2-derived prostanoids and oxidative stress additionally reduce endothelium-mediated relaxation in old type 2 diabetic rats. PLoS One. 2013; 8: e68217.
44. Barton M, Yanagisawa M, Vanhoutte PM, Masaki T. Endothelin XII. Life Sci. 2012; 91: 449–451.
45. Kalani M. The importance of endothelin-1 for microvascular dysfunction in diabetes. Vasc Health Risk Manag. 2008; 4: 1061–1068.
46. Abdelsaid M, Ma H, Coucha M, Ergul A. Late dual endothelin receptor blockade with bosentan restores impaired cerebrovascular function in diabetes. Life Sci. 2014; 118: 263–267.
47. Harris AK, Elgebaly MM, Li W, Sachidanandam K, Ergul A. Effect of chronic endothelin receptor antagonism on cerebrovascular function in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol. 2008; 294: R1213–R1219.
48. B receptor blockade improve endothelium-dependent vasodilatation in patients with type 2 diabetes and coronary artery disease. Life Sci. 2014; 118: 435–439.
49. Schreuder TH, van Lotringen JH, Hopman MT, Thijssen DH. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus. Exp Physiol. 2014; 99: 1253–1264.
50. Campia U, Tesauro M, Di Daniele N, Cardillo C. The vascular endothelin system in obesity and type 2 diabetes: Pathophysiology and therapeutic implications. Life Sci. 2014; 118: 149–155.
51. Liao JK. Linking endothelial dysfunction with endothelial cell activation. J Clin Invest. 2013; 123: 540–541.
52. Poittevin M, Bonnin P, Pimpie C et al. Diabetic microangiopathy: Impact of impaired cerebral vasoreactivity and delayed angiogenesis after permanent middle cerebral artery occlusion on stroke damage and cerebral repair in mice. Diabetes. 2015; 64: 999–1010.
53. Manasson J, Tien T, Moore C, Kumar NM, Roy S. High glucose-induced downregulation of connexin 30.2 promotes retinal vascular lesions: Implications for diabetic retinopathy. Invest Ophthalmol Vis Sci. 2013; 54: 2361–2366.
54. Tien T, Barrette KF, Chronopoulos A, Roy S. Effects of high glucose-induced cx43 downregulation on occludin and zo-1 expression and tight junction barrier function in retinal endothelial cells. Invest Ophthalmol Vis Sci. 2013; 54: 6518–6525.
55. Roy S, Kim D, Hernandez C, Simo R, Roy S. Beneficial effects of fenofibric acid on overexpression of extracellular matrix components, cox-2, and impairment of endothelial permeability associated with diabetic retinopathy. Exp Eye Res. 2015; 140: 124–129.
56. Goncalves A, Marques C, Leal E et al. Dipeptidyl peptidase-IV inhibition prevents blood–retinal barrier breakdown, inflammation and neuronal cell death in the retina of type 1 diabetic rats. Biochim Biophys Acta. 2014; 1842: 1454–1463.
57. 2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes. Proc Natl Acad Sci U S A. 2016; 113: 7213–7218.
58. Othman A, Ahmad S, Megyerdi S et al. 12/15-Lipoxygenase-derived lipid metabolites induce retinal endothelial cell barrier dysfunction: Contribution of NADPH oxidase. PLoS One. 2013; 8: e57254.
59. Li B, Li Y, Liu K et al. High glucose decreases claudins-5 and -11 in cardiac microvascular endothelial cells: Antagonistic effects of tongxinluo. Endocr Res. 2017; 42: 15–21.
60. Chapouly C, Yao Q, Vandierdonck S et al. Impaired hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: Implication in diabetes. Cardiovasc Res. 2016; 109: 217–227.
61. Molina-Jijon E, Rodriguez-Munoz R, Namorado Mdel C, Pedraza-Chaverri J, Reyes JL. Oxidative stress induces claudin-2 nitration in experimental type 1 diabetic nephropathy. Free Radic Biol Med. 2014; 72: 162–175.
62. Sajja RK, Prasad S, Cucullo L. Impact of altered glycaemia on blood–brain barrier endothelium: An in vitro study using the hCMEC/D3 cell line. Fluids Barriers CNS. 2014; 11: 8.
63. Boels MG, Avramut MC, Koudijs A et al. Atrasentan reduces albuminuria by restoring the glomerular endothelial glycocalyx barrier in diabetic nephropathy. Diabetes. 2016; 65: 2429–2439.
64. Singh A, Ramnath RD, Foster RR et al. Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One. 2013; 8: e55852.
65. Fu J, Lee K, Chuang PY, Liu Z, He JC. Glomerular endothelial cell injury and cross talk in diabetic kidney disease. Am J Physiol Renal Physiol. 2015; 308: F287–F297.
66. 3 integrin ligand occupancy inhibits the progression of albuminuria in diabetic rats. J Diabetes Res. 2014; 2014: 421827.
67. You JJ, Yang CH, Yang CM, Chen MS. Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin αvβ3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells. Cell Signal. 2014; 26: 133–140.
68. 1 integrin signaling in diabetic retinopathy. Diabetes. 2014; 63: 3057–3068.
69. Lee YJ, Jung SH, Kim SH et al. Essential role of transglutaminase 2 in vascular endothelial growth factor-induced vascular leakage in the retina of diabetic mice. Diabetes. 2016; 65: 2414–2428.
70. Abu El-Asrar AM, Mohammad G, Nawaz MI et al. The chemokine platelet factor-4 variant (PF-4var)/CXCL4L1 inhibits diabetes-induced blood–retinal barrier breakdown. Invest Ophthalmol Vis Sci. 2015; 56: 1956–1964.
71. Peng X, Chen R, Wu Y et al. PPARγ-PI3K/AKT-NO signal pathway is involved in cardiomyocyte hypertrophy induced by high glucose and insulin. J Diabetes Complicat. 2015; 29: 755–760.
72. Shida T, Nozawa T, Sobajima M, Ihori H, Matsuki A, Inoue H. Fluvastatin-induced reduction of oxidative stress ameliorates diabetic cardiomyopathy in association with improving coronary microvasculature. Heart Vessel. 2014; 29: 532–541.
73. Chiu AP, Wan A, Lal N et al. Cardiomyocyte VEGF regulates endothelial cell GPIHBP1 to relocate lipoprotein lipase to the coronary lumen during diabetes mellitus. Arterioscler Thromb Vasc Biol. 2016; 36: 145–155.
74. Tsukahara T, Tsukahara R, Haniu H, Matsuda Y, Murakami-Murofushi K. Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma. Mol Cell Endocrinol. 2015; 412: 320–329.
75. Lei S, Li H, Xu J et al. Hyperglycemia-induced protein kinase Cβ2 activation induces diastolic cardiac dysfunction in diabetic rats by impairing caveolin-3 expression and Akt/eNOS signaling. Diabetes. 2013; 62: 2318–2328.
76. Hou N, Huang N, Han F, Zhao J, Liu X, Sun X. Protective effects of adiponectin on uncoupling of glomerular VEGF–NO axis in early streptozotocin-induced type 2 diabetic rats. Int Urol Nephrol. 2014; 46: 2045–2051.
77. Advani A, Connelly KA, Advani SL et al. Role of the eNOS–NO system in regulating the antiproteinuric effects of VEGF receptor 2 inhibition in diabetes. Biomed Res Int. 2013; 2013: 201475.
78. 2b receptor inhibition on VEGF and nitric oxide axis-mediated renal function in diabetic nephropathy. Ren Fail. 2014; 36: 916–924.
79. Omae T, Nagaoka T, Tanano I, Yoshida A. Adiponectin-induced dilation of isolated porcine retinal arterioles via production of nitric oxide from endothelial cells. Invest Ophthalmol Vis Sci. 2013; 54: 4586–4594.
80. Takahashi T, Harris RC. Role of endothelial nitric oxide synthase in diabetic nephropathy: Lessons from diabetic eNOS knockout mice. J Diabetes Res. 2014; 2014: 590541.
81. Li Q, Atochin D, Kashiwagi S et al. Deficient eNOS phosphorylation is a mechanism for diabetic vascular dysfunction contributing to increased stroke size. Stroke. 2013; 44: 3183–3188.
82. Chandra SB, Mohan S, Ford BM et al. Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice. J Cereb Blood Flow Metab. 2016; 36: 1135–1142.
83. Baumgardt SL, Paterson M, Leucker TM et al. Chronic co-administration of sepiapterin and l-citrulline ameliorates diabetic cardiomyopathy and myocardial ischemia/reperfusion injury in obese type 2 diabetic mice. Circ Heart Fail. 2016; 9: e002424.
84. Claybaugh T, Decker S, McCall K et al. l-Arginine supplementation in type II diabetic rats preserves renal function and improves insulin sensitivity by altering the nitric oxide pathway. Int J Endocrinol. 2014; 2014: 171546.
85. You H, Gao T, Cooper TK, Morris SM Jr, Awad AS. Arginase inhibition: A new treatment for preventing progression of established diabetic nephropathy. Am J Physiol Renal Physiol. 2015; 309: F447–F455.
86. Hsu YC, Lee PH, Lei CC, Ho C, Shih YH, Lin CL. Nitric oxide donors rescue diabetic nephropathy through oxidative-stress- and nitrosative-stress-mediated wnt signaling pathways. J Diabetes Investig. 2015; 6: 24–34.
87. Kant V, Kumar D, Kumar D et al. Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats. Cytokine. 2015; 73: 144–155.
88. Bir SC, Pattillo CB, Pardue S et al. Nitrite anion therapy protects against chronic ischemic tissue injury in db/db diabetic mice in a NO/VEGF-dependent manner. Diabetes. 2014; 63: 270–281.
89. Kowluru RA, Kowluru A, Veluthakal R et al. TIAM1-RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia. 2014; 57: 1047–1056.
90. Alam NM, Mills WC 4th, Wong AA, Douglas RM, Szeto HH, Prusky GT. A mitochondrial therapeutic reverses visual decline in mouse models of diabetes. Dis Model Mech. 2015; 8: 701–710.
91. Yang JT, Qian LB, Zhang FJ et al. Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway. J Cardiovasc Pharmacol. 2015; 65: 349–356.
92. 2 promotes aberrant retinal neovascularization via activation of VEGF receptor 2 pathway in oxygen-induced retinopathy. J Diabetes Res. 2015; 2015: 963289.
93. Wong CM, Zhang Y, Huang Y. Bone morphogenic protein-4-induced oxidant signaling via protein carbonylation for endothelial dysfunction. Free Radic Biol Med. 2014; 75: 178–190.
94. Wang G, Li W, Chen Q, Jiang Y, Lu X, Zhao X. Hydrogen sulfide accelerates wound healing in diabetic rats. Int J Clin Exp Pathol. 2015; 8: 5097–5104.
95. Leguina-Ruzzi A, Pereira J, Pereira-Flores K et al. Increased RhoA/Rho-kinase activity and markers of endothelial dysfunction in young adult subjects with metabolic syndrome. Metab Syndr Relat Disord. 2015; 13: 373–380.
96. Wu J, Liang Z, Zhou J et al. Association of biomarkers of inflammation and endothelial dysfunction with fasting and postload glucose metabolism: A population-based prospective cohort study among Inner Mongolians in China. Can J Diabetes. 2016; 40: 509–514.
97. Fukui M, Tanaka M, Senmaru T et al. Lox-1 is a novel marker for peripheral artery disease in patients with type 2 diabetes. Metabolism. 2013; 62: 935–938.
98. Gao Q, Fan Y, Mu LY, Ma L, Song ZQ, Zhang YN. S100b and ADMA in cerebral small vessel disease and cognitive dysfunction. J Neurol Sci. 2015; 354: 27–32.
99. Savage SR, Bretz CA, Penn JS. RNA-seq reveals a role for NFAT-signaling in human retinal microvascular endothelial cells treated with TNFalpha. PLoS One. 2015; 10: e0116941.
100. Zhang L, Dong L, Liu X et al. Alpha-melanocyte-stimulating hormone protects retinal vascular endothelial cells from oxidative stress and apoptosis in a rat model of diabetes. PLoS One. 2014; 9: e93433.
101. Pavkov ME, Weil EJ, Fufaa GD et al. Tumor necrosis factor receptors 1 and 2 are associated with early glomerular lesions in type 2 diabetes. Kidney Int. 2016; 89: 226–234.
102. Portillo JA, Schwartz I, Zarini S et al. Proinflammatory responses induced by CD40 in retinal endothelial and Müller cells are inhibited by blocking CD40-Traf2,3 or CD40-Traf6 signaling. Invest Ophthalmol Vis Sci. 2014; 55: 8590–8597.
103. Portillo JA, Greene JA, Okenka G et al. Cd40 promotes the development of early diabetic retinopathy in mice. Diabetologia. 2014; 57: 2222–2231.
104. Abu El-Asrar AM, De Hertogh G, Nawaz MI et al. The tumor necrosis factor superfamily members TWEAK, TNFSF15 and fibroblast growth factor-inducible protein 14 are upregulated in proliferative diabetic retinopathy. Ophthalmic Res. 2015; 53: 122–130.
105. Zhang Q, Steinle JJ. IGFBP-3 inhibits TNF-alpha production and TNFR-2 signaling to protect against retinal endothelial cell apoptosis. Microvasc Res. 2014; 95: 76–81.
106. Jiang F, Chen Q, Huang L et al. TNFSF15 inhibits blood retinal barrier breakdown induced by diabetes. Int J Mol Sci. 2016; 17: E615. doi:10.3390/ijms17050615.
107. Arita R, Nakao S, Kita T et al. A key role for Rock in TNF-alpha-mediated diabetic microvascular damage. Invest Ophthalmol Vis Sci. 2013; 54: 2373–2383.
108. Utkan T, Yazir Y, Karson A, Bayramgurler D. Etanercept improves cognitive performance and increases eNOS and BDNF expression during experimental vascular dementia in streptozotocin-induced diabetes. Curr Neurovasc Res. 2015; 12: 135–146.
109. Chou JC, Rollins SD, Ye M, Batlle D, Fawzi AA. Endothelin receptor-A antagonist attenuates retinal vascular and neuroretinal pathology in diabetic mice. Invest Ophthalmol Vis Sci. 2014; 55: 2516–2525.
110. B endothelin receptor antagonist, in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats. Pharmacol Biochem Behav. 2014; 124: 27–35.
111. Li X, Wu TT, Chen J, Qiu W. Elevated expression levels of serum insulin-like growth factor-1, tumor necrosis factor-alpha and vascular endothelial growth factor 165 might exacerbate type 2 diabetic nephropathy. J Diabetes Investig. 2016; 8: 108–114.
112. Rodrigues M, Xin X, Jee K et al. VEGF secreted by hypoxic Muller cells induces MMP-2 expression and activity in endothelial cells to promote retinal neovascularization in proliferative diabetic retinopathy. Diabetes. 2013; 62: 3863–3873.
113. Do JY, Choi YK, Kook H, Suk K, Lee IK, Park DH. Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor gamma. Biochem Biophys Res Commun. 2015; 460: 457–463.
114. Taylor SL, Trudeau D, Arnold B et al. VEGF can protect against blood brain barrier dysfunction, dendritic spine loss and spatial memory impairment in an experimental model of diabetes. Neurobiol Dis. 2015; 78: 1–11.
115. Costa R, Negrao R, Valente I et al. Xanthohumol modulates inflammation, oxidative stress, and angiogenesis in type 1 diabetic rat skin wound healing. J Nat Prod. 2013; 76: 2047–2053.
116. Takeda K, Duan LJ, Takeda H, Fong GH. Improved vascular survival and growth in the mouse model of hindlimb ischemia by a remote signaling mechanism. Am J Pathol. 2014; 184: 686–696.
117. Feng B, Cao Y, Chen S, Chu X, Chu Y, Chakrabarti S. MiR-200b mediates endothelial-to-mesenchymal transition in diabetic cardiomyopathy. Diabetes. 2016; 65: 768–779.
118. Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and no production in human endothelial cells. Am J Phys. 1998; 274: H1054–H1058.
119. van der Zee R, Murohara T, Luo Z et al. Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation. 1997; 95: 1030–1037.
120. Cooke JP, Losordo DW. Nitric oxide and angiogenesis. Circulation. 2002; 105: 2133–2135.
121. Ziche M, Morbidelli L, Choudhuri R et al. Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest. 1997; 99: 2625–2634.
122. Ulker E, Parker WH, Raj A, Qu ZC, May JM. Ascorbic acid prevents VEGF-induced increases in endothelial barrier permeability. Mol Cell Biochem. 2016; 412: 73–79.
123. Yu CG, Zhang N, Yuan SS et al. Endothelial progenitor cells in diabetic microvascular complications: Friends or foes? Stem Cells Int. 2016; 2016: 1803989.
124. Jeansson M, Gawlik A, Anderson G et al. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest. 2011; 121: 2278–2289.
125. Gnudi L. Angiopoietins and diabetic nephropathy. Diabetologia. 2016; 59: 1616–1620.
126. Fagiani E, Christofori G. Angiopoietins in angiogenesis. Cancer Lett. 2013; 328: 18–26.
127. Dessapt-Baradez C, Woolf AS, White KE et al. Targeted glomerular angiopoietin-1 therapy for early diabetic kidney disease. J Am Soc Nephrol. 2014; 25: 33–42.
128. Yamamoto Y, Maeshima Y, Kitayama H et al. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy. Diabetes. 2004; 53: 1831–1840.
129. Qiu Y, Zhao D, Butenschon VM et al. Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. Acta Diabetol. 2016; 53: 81–89.
130. Luo C, Li T, Zhang C et al. Therapeutic effect of alprostadil in diabetic nephropathy: Possible roles of angiopoietin-2 and IL-18. Cell Physiol Biochem. 2014; 34: 916–928.
131. You QY, Zhuge FY, Zhu QQ, Si XW. Effects of laser photocoagulation on serum angiopoietin-1, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, and soluble angiopoietin receptor Tie-2 levels in type 2 diabetic patients with proliferative diabetic retinopathy. Int J Ophthalmol. 2014; 7: 648–653.
132. Khairoun M, van den Heuvel M, van den Berg BM et al. Early systemic microvascular damage in pigs with atherogenic diabetes mellitus coincides with renal angiopoietin dysbalance. PLoS One. 2015; 10: e0121555.
133. Cahoon JM, Rai RR, Carroll LS et al. Intravitreal AAV2.COMP-Ang1 prevents neurovascular degeneration in a murine model of diabetic retinopathy. Diabetes. 2015; 64: 4247–4259.
134. Yokouchi H, Eto K, Nishimura W et al. Angiopoietin-like protein 4 (ANGPTL4) is induced by high glucose in retinal pigment epithelial cells and exhibits potent angiogenic activity on retinal endothelial cells. Acta Ophthalmol. 2013; 91: e289–e297.
135. Babapoor-Farrokhran S, Jee K, Puchner B et al. Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy. Proc Natl Acad Sci U S A. 2015; 112: E3030–E3039.
136. Tesfamariam B. Endothelial repair and regeneration following intimal injury. J Cardiovasc Transl Res. 2016; 9: 91–101.
137. Hofmann M, Wollert KC, Meyer GP et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation. 2005; 111: 2198–2202.
138. Mingliang R, Bo Z, Zhengguo W. Stem cells for cardiac repair: Status, mechanisms, and new strategies. Stem Cells Int. 2011; 2011: 310928.
139. Rigato M, Bittante C, Albiero M, Avogaro A, Fadini GP. Circulating progenitor cell count predicts microvascular outcomes in type 2 diabetic patients. J Clin Endocrinol Metab. 2015; 100: 2666–2672.
140. Bitterli L, Afan S, Buhler S et al. Endothelial progenitor cells as a biological marker of peripheral artery disease. Vasc Med. 2016; 21: 3–11.
141. Wang F, Guo X, Shen X, Kream RM, Mantione KJ, Stefano GB. Vascular dysfunction associated with type 2 diabetes and Alzheimer’s disease: A potential etiological linkage. Med Sci Monit Basic Res. 2014; 20: 118–129.
142. Lutz AH, Blumenthal JB, Landers-Ramos RQ, Prior SJ. Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes. J Appl Physiol (1985). 2016; 121: 36–41.
143. Jarajapu YP, Hazra S, Segal M et al. Vasoreparative dysfunction of cd34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms. PLoS One. 2014; 9: e93965.
144. Yuan Q, Hu CP, Gong ZC et al. Accelerated onset of senescence of endothelial progenitor cells in patients with type 2 diabetes mellitus: Role of dimethylarginine dimethylaminohydrolase 2 and asymmetric dimethylarginine. Biochem Biophys Res Commun. 2015; 458: 869–876.
145. Zhu G, Wang J, Song M et al. Irisin increased the number and improved the function of endothelial progenitor cells in diabetes mellitus mice. J Cardiovasc Pharmacol. 2016; 68: 67–73.
146. Liu J, Hao H, Xia L et al. Hypoxia pretreatment of bone marrow mesenchymal stem cells facilitates angiogenesis by improving the function of endothelial cells in diabetic rats with lower ischemia. PLoS One. 2015; 10: e0126715.
147. Li X, Gan K, Song G, Wang C. VEGF gene transfected umbilical cord mesenchymal stem cells transplantation improve the lower limb vascular lesions of diabetic rats. J Diabetes Complicat. 2015; 29: 872–881.
148. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001; 294: 853–858.
149. Zampetaki A, Kiechl S, Drozdov I et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010; 107: 810–817.
150. Silambarasan M, Tan JR, Karolina DS, Armugam A, Kaur C, Jeyaseelan K. MicroRNAs in hyperglycemia induced endothelial cell dysfunction. Int J Mol Sci. 2016; 17: 518.
151. Witkowski M, Weithauser A, Tabaraie T et al. Micro-RNA-126 reduces the blood thrombogenicity in diabetes mellitus via targeting of tissue factor. Arterioscler Thromb Vasc Biol. 2016; 36: 1263–1271.
152. Mocharla P, Briand S, Giannotti G et al. AngiomiR-126 expression and secretion from circulating CD34(+) and CD14(+) PBMCs: Role for proangiogenic effects and alterations in type 2 diabetics. Blood. 2013; 121: 226–236.
153. Mortuza R, Feng B, Chakrabarti S. MiR-195 regulates sirt1-mediated changes in diabetic retinopathy. Diabetologia. 2014; 57: 1037–1046.
154. Zheng D, Ma J, Yu Y et al. Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia. 2015; 58: 1949–1958.
155. Borradaile NM, Pickering JG. Nad(+), sirtuins, and cardiovascular disease. Curr Pharm Des. 2009; 15: 110–117.
156. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and sirt1. Nature. 2005; 434: 113–118.
157. McArthur K, Feng B, Wu Y, Chen S, Chakrabarti S. MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes. 2011; 60: 1314–1323.
158. Zhang H, Liu J, Qu D et al. Inhibition of miR-200c restores endothelial function in diabetic mice through suppression of cox-2. Diabetes. 2016; 65: 1196–1207.
159. Wang HJ, Huang YL, Shih YY, Wu HY, Peng CT, Lo WY. MicroRNA-146a decreases high glucose/thrombin-induced endothelial inflammation by inhibiting NAPDH oxidase 4 expression. Mediat Inflamm. 2014; 2014: 379537.
160. Fulzele S, El-Sherbini A, Ahmad S et al. MicroRNA-146b-3p regulates retinal inflammation by suppressing adenosine deaminase-2 in diabetes. Biomed Res Int. 2015; 2015: 846501.
161. Baldeon RL, Weigelt K, de Wit H et al. Decreased serum level of miR-146a as sign of chronic inflammation in type 2 diabetic patients. PLoS One. 2014; 9: e115209.
162. La Sala L, Cattaneo M, De Nigris V et al. Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells. Cardiovasc Diabetol. 2016; 15: 71.
163. Zhong X, Liao Y, Chen L et al. The microRNAs in the pathogenesis of metabolic memory. Endocrinology. 2015; 156: 3157–3168.
164. Dong RP, Tachibana K, Hegen M et al. Determination of adenosine deaminase binding domain on cd26 and its immunoregulatory effect on T cell activation. J Immunol. 1997; 159: 6070–6076.
165. Caporali A, Meloni M, Vollenkle C et al. Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation. 2011; 123: 282–291.
166. Caporali A, Meloni M, Nailor A et al. P75(NTR)-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte–endothelial crosstalk in diabetes after limb ischaemia. Nat Commun. 2015; 6: 8024.
167. Ye M, Li D, Yang J et al. MicroRNA-130a targets MAP3K12 to modulate diabetic endothelial progenitor cell function. Cell Physiol Biochem. 2015; 36: 712–726.
168. Xu Q, Meng S, Liu B et al. MicroRNA-130a regulates autophagy of endothelial progenitor cells through runx3. Clin Exp Pharmacol Physiol. 2014; 41: 351–357.
169. Bhatia P, Raina S, Chugh J, Sharma S. MiRNAs: Early prognostic biomarkers for type 2 diabetes mellitus? Biomark Med. 2015; 9: 1025–1040.
170. Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Eur Heart J. 2013; 34: 2436–2443.
171. Ceriello A, Novials A, Ortega E et al. Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls. Nutr Metab Cardiovasc Dis. 2014; 24: 116–123.
172. Zhang XG, Zhang YQ, Zhao DK et al. Relationship between blood glucose fluctuation and macrovascular endothelial dysfunction in type 2 diabetic patients with coronary heart disease. Eur Rev Med Pharmacol Sci. 2014; 18: 3593–3600.
173. Luna P, Guarner V, Farias JM, Hernandez-Pacheco G, Martinez M. Importance of metabolic memory in the development of vascular complications in diabetic patients. J Cardiothorac Vasc Anesth. 2016; 30: 1369–1378.
174. An H, Wei R, Ke J et al. Metformin attenuates fluctuating glucose-induced endothelial dysfunction through enhancing GTPCH1-mediated eNOS recoupling and inhibiting NADPH oxidase. J Diabetes Complicat. 2016; 30: 1017–1024.
175. Santos JM, Mishra M, Kowluru RA. Posttranslational modification of mitochondrial transcription factor A in impaired mitochondria biogenesis: Implications in diabetic retinopathy and metabolic memory phenomenon. Exp Eye Res. 2014; 121: 168–177.
176. Desiderio A, Spinelli R, Ciccarelli M et al. Epigenetics: Spotlight on type 2 diabetes and obesity. J Endocrinol Investig. 2016; 39: 1095–1103.
177. Muka T, Koromani F, Portilla E et al. The role of epigenetic modifications in cardiovascular disease: A systematic review. Int J Cardiol. 2016; 212: 174–183.
178. Hosseinzadeh-Attar M, Kolahdouz Mohammadi R, Eshraghian M et al. Reduction in asymmetric dimethylarginine plasma levels by coenzyme Q10 supplementation in patients with type 2 diabetes mellitus. Minerva Endocrinol. 2015; 40: 259–266.
179. Shemyakin A, Kovamees O, Rafnsson A et al. Arginase inhibition improves endothelial function in patients with coronary artery disease and type 2 diabetes mellitus. Circulation. 2012; 126: 2943–2950.
180. Katakam PV, Ujhelyi MR, Hoenig M, Miller AW. Metformin improves vascular function in insulin-resistant rats. Hypertension. 2000; 35: 108–112.
181. Pitocco D, Zaccardi F, Tarzia P et al. Metformin improves endothelial function in type 1 diabetic subjects: A pilot, placebo-controlled randomized study. Diabetes Obes Metab. 2013; 15: 427–431.
182. Yu JW, Deng YP, Han X, Ren GF, Cai J, Jiang GJ. Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice. Cardiovasc Diabetol. 2016; 15: 88.
183. Shah GN, Morofuji Y, Banks WA, Price TO. High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes. Biochem Biophys Res Commun. 2013; 440: 354–358.
184. Szwejkowski BR, Gandy SJ, Rekhraj S et al. Allopurinol reduces left ventricular mass in patients with type 2 diabetes and left ventricular hypertrophy. J Am Coll Cardiol. 2013; 62: 2284–2293.
185. Duscher D, Neofytou E, Wong VW et al. Transdermal deferoxamine prevents pressure-induced diabetic ulcers. Proc Natl Acad Sci U S A. 2015; 112: 94–99.
186. Khajehdehi P, Pakfetrat M, Javidnia K et al. Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-beta and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: A randomized, double-blind and placebo-controlled study. Scand J Urol Nephrol. 2011; 45: 365–370.
187. Pena AS, Maftei O, Dowling K et al. Folate fortification and supplementation do not provide vascular health benefits in type 1 diabetes. J Pediatr. 2013; 163: 255–260.
188. Shi Y, Cosentino F, Camici GG et al. Oxidized low-density lipoprotein activates p66shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase C-beta, and c-jun N-terminal kinase kinase in human endothelial cells. Arterioscler Thromb Vasc Biol. 2011; 31: 2090–2097.
189. Jenkins AJ, Joglekar MV, Hardikar AA, Keech AC, O’Neal DN, Januszewski AS. Biomarkers in diabetic retinopathy. Rev Diabet Stud. 2015; 12: 159–195.
190. Hsieh CJ, Wang PW. Effect of cilostazol treatment on adiponectin and soluble cd40 ligand levels in diabetic patients with peripheral arterial occlusion disease. Circ J. 2009; 73: 948–954.
191. Tani N, Hada K, Kitami A et al. Effects of acetyl salicylic acid and cilostazol administration on serum thrombomodulin concentration in diabetic patients. Thromb Res. 1993; 69: 153–158.
192. Tsutsui M, Shimokawa H, Higuchi S et al. Effect of cilostazol, a novel anti-platelet drug, on restenosis after percutaneous transluminal coronary angioplasty. Jpn Circ J. 1996; 60: 207–215.
193. Ueno H, Koyama H, Mima Y et al. Comparison of the effect of cilostazol with aspirin on circulating endothelial progenitor cells and small-dense LDL cholesterol in diabetic patients with cerebral ischemia: A randomized controlled pilot trial. J Atheroscler Thromb. 2011; 18: 883–890.
194. Biscetti F, Pecorini G, Arena V et al. Cilostazol improves the response to ischemia in diabetic mice by a mechanism dependent on PPARgamma. Mol Cell Endocrinol. 2013; 381: 80–87.
195. Suzuki K, Uchida K, Nakanishi N, Hattori Y. Cilostazol activates AMP-activated protein kinase and restores endothelial function in diabetes. Am J Hypertens. 2008; 21: 451–457.
196. Ota H, Eto M, Kano MR et al. Cilostazol inhibits oxidative stress-induced premature senescence via upregulation of sirt1 in human endothelial cells. Arterioscler Thromb Vasc Biol. 2008; 28: 1634–1639.
197. Gao L, Wang F, Wang B et al. Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell adhesion molecule-1 expression. J Pharmacol Exp Ther. 2006; 318: 53–58.
198. Drucker DJ, Nauck MA. The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368: 1696–1705.
199. Fukuda S, Nakagawa S, Tatsumi R et al. Glucagon-like peptide-1 strengthens the barrier integrity in primary cultures of rat brain endothelial cells under basal and hyperglycemia conditions. J Mol Neurosci. 2016; 59: 211–219.
200. Wang D, Luo P, Wang Y et al. Glucagon-like peptide-1 protects against cardiac microvascular injury in diabetes via a cAMP/PKA/Rho-dependent mechanism. Diabetes. 2013; 62: 1697–1708.
201. Ojima A, Ishibashi Y, Matsui T et al. Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end product-induced protein arginine methyltranferase-1 expression. Am J Pathol. 2013; 182: 132–141.
202. Alter ML, Ott IM, von Websky K et al. DPP-4 inhibition on top of angiotensin receptor blockade offers a new therapeutic approach for diabetic nephropathy. Kidney Blood Press Res. 2012; 36: 119–130.
203. Kanasaki K, Shi S, Kanasaki M et al. Linagliptin-mediated dpp-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes. 2014; 63: 2120–2131.
204. Terawaki Y, Nomiyama T, Kawanami T et al. Dipeptidyl peptidase-4 inhibitor linagliptin attenuates neointima formation after vascular injury. Cardiovasc Diabetol. 2014; 13: 154.
205. Goto H, Nomiyama T, Mita T et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury. Biochem Biophys Res Commun. 2011; 405: 79–84.
206. Murthy SN, Hilaire RC, Casey DB et al. The synthetic GLP-I receptor agonist, exenatide, reduces intimal hyperplasia in insulin resistant rats. Diab Vasc Dis Res. 2010; 7: 138–144.
207. Fadini GP, Boscaro E, Albiero M et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: Possible role of stromal-derived factor-1alpha. Diabetes Care. 2010; 33: 1607–1609.
208. Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism. 2014; 63: 1141–1148.
209. Olver TD, McDonald MW, Grise KN et al. Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes. Am J Physiol Regul Integr Comp Physiol. 2014; 306: R941–R950.
210. Kleindienst A, Battault S, Belaidi E et al. Exercise does not activate the β3 adrenergic receptor–eNOS pathway, but reduces inducible NOS expression to protect the heart of obese diabetic mice. Basic Res Cardiol. 2016; 111: 40.
211. Sonobe T, Tsuchimochi H, Schwenke DO, Pearson JT, Shirai M. Treadmill running improves hindlimb arteriolar endothelial function in type 1 diabetic mice as visualized by X-ray microangiography. Cardiovasc Diabetol. 2015; 14: 51.
212. Trevellin E, Scorzeto M, Olivieri M et al. Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes. 2014; 63: 2800–2811.
213. Olver TD, Laughlin MH. Endurance, interval sprint, and resistance exercise training: Impact on microvascular dysfunction in type 2 diabetes. Am J Physiol Heart Circ Physiol. 2016; 310: H337–H350.