title: Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing.
abstract: This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres.
authors: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
authors: Anton J M
authors: AJ
authors: Wagenmakers
authors: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
authors: Juliette A
authors: JA
authors: Strauss
authors: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
authors: Sam O
authors: SO
authors: Shepherd
authors: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
authors: Michelle A
authors: MA
authors: Keske
authors: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK.
authors: Matthew
authors: M
authors: Cocks
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability; D004435:Eating; D004730:Endothelium, Vascular / Q000378:metabolism*; D015444:Exercise; D006801:Humans; D007328:Insulin / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D007328:Insulin
references: J Physiol. 1919 May 20;52(6):409-15
references: 16993405
references: Circ Res. 1980 Sep;47(3):301-11
references: 6996862
references: Endocr Rev. 2007 Aug;28(5):463-91
references: 17525361
references: Microvasc Res. 1988 Sep;36(2):162-71
references: 3185308
references: Diabetes. 1997 Sep;46(9):1381-8
references: 9287035
references: Exp Physiol. 2013 Dec;98 (12 ):1645-58
references: 23995101
references: Diabetes. 2006 May;55(5):1436-42
references: 16644702
references: Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E252-63
references: 21610226
references: Annu Rev Biomed Eng. 2007;9:121-67
references: 17373886
references: J Clin Invest. 1985 Jul;76(1):149-55
references: 3894418
references: Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H1916-23
references: 10843889
references: Physiol Rep. 2014 Jul 22;2(7):null
references: 25052490
references: Pflugers Arch. 2007 Jun;454(3):345-59
references: 17256154
references: J Lipid Res. 2004 Apr;45(4):603-9
references: 14729862
references: Mol Endocrinol. 2009 Oct;23(10):1613-23
references: 19608646
references: Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1191-7
references: 16682488
references: J Clin Endocrinol Metab. 2003 Oct;88(10):4559-64
references: 14557422
references: Microcirculation. 2013 Feb;20(2):117-37
references: 23025284
references: Microcirculation. 2012 Oct;19(7):642-51
references: 22642427
references: Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E134-44
references: 20959538
references: Clin Orthop Relat Res. 2009 Apr;467(4):1074-82
references: 18972175
references: Mol Endocrinol. 2012 Aug;26(8):1327-38
references: 22734037
references: J Biol Chem. 2012 Jul 6;287(28):23502-16
references: 22584574
references: Am J Cardiol. 1988 Sep 9;62(8):30E-35E
references: 3414535
references: Curr Diab Rep. 2003 Aug;3(4):279-88
references: 12866989
references: J Physiol. 1985 Sep;366:233-49
references: 4057091
references: Physiol Rev. 2003 Jan;83(1):183-252
references: 12506130
references: Diabetes. 2004 Jun;53(6):1418-23
references: 15161743
references: J Appl Physiol (1985). 1989 Jul;67(1):291-9
references: 2759955
references: Microcirculation. 2014 May;21(4):301-14
references: 24450403
references: Diabetes. 2007 Jan;56(1):168-76
references: 17192479
references: J Physiol. 2000 Apr 1;524 Pt 1:267-78
references: 10747197
references: J Physiol. 2001 Oct 1;536(Pt 1):295-304
references: 11579177
references: JAMA. 2007 Jul 18;298(3):309-16
references: 17635891
references: J Clin Endocrinol Metab. 2005 Feb;90(2):1078-82
references: 15536160
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1255-65
references: 21724864
references: Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E323-32
references: 16569759
references: Am J Physiol Regul Integr Comp Physiol. 2012 Dec;303(11):R1110-26
references: 22972834
references: Essays Biochem. 2006;42:193-210
references: 17144889
references: Diabetes. 1983 Jul;32(7):675-9
references: 6862113
references: Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2549-57
references: 23968980
references: Int J Microcirc Clin Exp. 1987;5(4):359-72
references: 3557821
references: Acta Physiol Scand Suppl. 1983;525:1-40
references: 6588730
references: Diabetes. 2013 Dec;62(12):4030-42
references: 23863813
references: Exp Physiol. 2014 Dec 1;99(12):1552-8
references: 25192730
references: Clin Orthop Relat Res. 1983 Oct;(179):275-83
references: 6617027
references: J Physiol. 2013 Feb 1;591(3):641-56
references: 22946099
references: J Clin Invest. 1995 Sep;96(3):1382-8
references: 7544802
references: Circ Res. 2003 Jul 11;93(1):61-8
references: 12791708
references: J Physiol. 2009 Jun 1;587(Pt 11):2579-88
references: 19403615
references: Diabetes. 2005 Jan;54(1):1-7
references: 15616004
references: J Physiol. 2016 Apr 15;594(8):2223-31
references: 25581640
references: Diabetologia. 2009 May;52(5):752-64
references: 19283361
references: Ann N Y Acad Sci. 1977;301:3-29
references: 73362
references: Microcirculation. 2005 Jan-Feb;12(1):33-45
references: 15804972
references: Circ Res. 2005 May 13;96(9):939-49
references: 15890981
references: Diabetes. 1996 Nov;45(11):1471-7
references: 8866549
references: Diabetes. 2008 Mar;57(3):540-7
references: 17977956
references: Diabetes Care. 2009 Sep;32(9):1672-7
references: 19487636
references: Diabetes Care. 2009 Nov;32 Suppl 2:S194-8
references: 19875551
references: Nature. 2010 Apr 8;464(7290):917-21
references: 20228789
references: Rev Physiol Biochem Pharmacol. 1977;77:149-209
references: 320642
references: J Appl Physiol (1985). 1993 Oct;75(4):1911-6
references: 8282650
references: J Physiol. 2009 Aug 1;587(Pt 15):3911-20
references: 19505983
references: J Physiol. 2001 Nov 1;536(Pt 3):937-46
references: 11691885
references: Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H2009-19
references: 17189352
references: Physiol Rev. 2010 Jan;90(1):367-417
references: 20086080
references: Circulation. 2013 Jan 1;127(1):86-95
references: 23204109