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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Modulation of Small Artery Function by Insulin in Young Women: Role of Adiposity

Author(s): Moulinath Banerjee*, Linda Shaw, Valentyn Charlton-Menys, Phillip Pemberton, Rayaz Ahmed Malik, John Kennedy Cruickshank and Clare Elizabeth Austin

Volume 20, Issue 8, 2020

Page: [1244 - 1252] Pages: 9

DOI: 10.2174/1871530320666200428111924

Price: $65

Abstract

Objectives: Vascular dysfunction is common in obesity. Insulin can directly modulate arterial function, but its role is unclear in obesity. We examined the influence of adiposity on direct effects of insulin on human artery responses.

Methods: 22 healthy women were stratified by median BMI into lower (LA) (n=11) and higher adiposity (HA) (n=11). Small arteries from gluteal biopsies were tested for contractile responses to Noradrenaline (NA), the endothelium-dependent dilator Carbachol and the endothelium-independent dilator sodium nitroprusside were examined before and after incubation with 100 mU/ml human insulin.

Results: Contractile responses were similar in the two groups. Insulin reduced NA-induced contraction in HA [3.5 (2.4-4.6) vs. 2.4 (1.4-3.4) mN/mm: p=0.004] but not those from LA [4.1 (2.8-5.3) vs. 3.7 (2.5-5.0) mN/mm: p=0.33]. Endothelium-dependent dilation (EDD) was significantly reduced in arteries from women in the HA (34.7 (18.8-50.6%)) compared to those from women in the LA (62.3 (46.2- 78.4); p=0.013). Insulin improved EDD (change in maximal dilation before/after insulin (%)) in arteries from the HA (37.7 (18.0 to 57.3) but not the LA (6.3 (-6.5 to 19.1), p=0.007.

Conclusion: Reduced EDD evident in arteries from HA subjects improve by incubating in insulin. Hyperinsulinaemia may be necessary in maintaining endothelial function in obesity.

Keywords: Small artery function, endothelium, insulin, adiposity, women, myography.

Graphical Abstract
[1]
Schwarz, P.E.; Reimann, M.; Li, J.; Bergmann, A.; Licinio, J.; Wong, M.L.; Bornstein, S.R. The Metabolic Syndrome - A global challenge for prevention. Horm. Metab. Res., 2007, 39(11), 777-780.
[http://dx.doi.org/10.1055/s-2007-990312] [PMID: 17992630]
[2]
Doll, R. Chronic and degenerative disease: Major causes of morbidity and death. Am. J. Clin. Nutr., 1995, 62(Suppl. 6), 1301S-1305S.
[http://dx.doi.org/10.1093/ajcn/62.6.1301S] [PMID: 7495224]
[3]
Levenson, J.W.; Skerrett, P.J.; Gaziano, J.M. Reducing the global burden of cardiovascular disease: the role of risk factors. Prev. Cardiol., 2002, 5(4), 188-199.
[http://dx.doi.org/10.1111/j.1520-037X.2002.00564.x] [PMID: 12417828]
[4]
Schalkwijk, C.G.; Stehouwer, C.D. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin. Sci. (Lond.), 2005, 109(2), 143-159.
[http://dx.doi.org/10.1042/CS20050025] [PMID: 16033329]
[5]
Adachi, H.; Goetz, F.C.; Jacobs, D.R.; Tsuruta, M.; Hirai, Y.; Fujiura, Y.; Imaizumi, T. The role of obesity in the association of cardiovascular risk factors and glucose intolerance in small Japanese and North American communities. Diabetes Res. Clin. Pract., 2000, 49(1), 41-51.
[http://dx.doi.org/10.1016/S0168-8227(00)00133-9] [PMID: 10808062]
[6]
de Lusignan, S.; Hague, N.; van Vlymen, J.; Dhoul, N.; Chan, T.; Thana, L.; Kumarapeli, P. A study of cardiovascular risk in overweight and obese people in England. Eur. J. Gen. Pract., 2006, 12(1), 19-29.
[http://dx.doi.org/10.1080/13814780600757260] [PMID: 16945868]
[7]
Wheatcroft, S.B.; Williams, I.L.; Shah, A.M.; Kearney, M.T. Pathophysiological implications of insulin resistance on vascular endothelial function. 2003, 20(4), 255-268.
[http://dx.doi.org/10.1046/j.1464-5491.2003.00869.x]
[8]
Baron, A.D. Insulin resistance and vascular function. J. Diabetes Complications, 2002, 16(1), 92-102.
[http://dx.doi.org/10.1016/S1056-8727(01)00209-4] [PMID: 11872375]
[9]
Hollmann, M.; Runnebaum, B.; Gerhard, I. Impact of waist-hip-ratio and body-mass-index on hormonal and metabolic parameters in young, obese women. Int. J. Obes. Relat. Metab. Disord., 1997, 21(6), 476-483.
[http://dx.doi.org/10.1038/sj.ijo.0800433] [PMID: 9192231]
[10]
Zavaroni, I.; Bonini, L.; Fantuzzi, M.; Dall’Aglio, E.; Passeri, M.; Reaven, G.M. Hyperinsulinaemia, obesity, and syndrome X. J. Intern. Med., 1994, 235(1), 51-56.
[http://dx.doi.org/10.1111/j.1365-2796.1994.tb01031.x] [PMID: 8283160]
[11]
Jonk, A.M.; Houben, A.J.; Schaper, N.C.; de Leeuw, P.W.; Serné, E.H.; Smulders, Y.M.; Stehouwer, C.D. Obesity is associated with impaired endothelial function in the postprandial state. Microvasc. Res., 2011, 82(3), 423-429.
[http://dx.doi.org/10.1016/j.mvr.2011.08.006] [PMID: 21875604]
[12]
Olson, T.P.; Schmitz, K.H.; Leon, A.S.; Dengel, D.R. Vascular structure and function in women: Relationship with body mass index. Am. J. Prev. Med., 2006, 30(6), 487-492.
[http://dx.doi.org/10.1016/j.amepre.2006.02.006] [PMID: 16704942]
[13]
Campia, U.; Tesauro, M.; Cardillo, C. Human obesity and endothelium-dependent responsiveness. Br. J. Pharmacol., 2012, 165(3), 561-573.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01661.x] [PMID: 21895631]
[14]
Misurski, D.A.; Wu, S.Q.; McNeill, J.R.; Wilson, T.W.; Gopalakrishnan, V. Insulin-induced biphasic responses in rat mesenteric vascular bed: role of endothelin. Hypertension, 2001, 37(5), 1298-1302.
[http://dx.doi.org/10.1161/01.HYP.37.5.1298] [PMID: 11358944]
[15]
Izhar, U.; Hasdai, D.; Richardson, D.M.; Cohen, P.; Lerman, A. Insulin and insulin-like growth factor-I cause vasorelaxation in human vessels in vitro. Coron. Artery Dis., 2000, 11(1), 69-76.
[http://dx.doi.org/10.1097/00019501-200002000-00012] [PMID: 10715809]
[16]
Ferri, C.; De Mattia, G. The effect of insulin on endothelin-1 (ET-1) secretion in human cultured endothelial cell. Metabolism, 1995, 44(5), 689-690.
[http://dx.doi.org/10.1016/0026-0495(95)90130-2] [PMID: 7752921]
[17]
Hartell, N.A.; Archer, H.E.; Bailey, C.J. Insulin-stimulated endothelial nitric oxide release is calcium independent and mediated via protein kinase B. Biochem. Pharmacol., 2005, 69(5), 781-790.
[http://dx.doi.org/10.1016/j.bcp.2004.11.022] [PMID: 15710355]
[18]
Montagnani, M.; Ravichandran, L.V.; Chen, H.; Esposito, D.L.; Quon, M.J. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol. Endocrinol., 2002, 16(8), 1931-1942.
[http://dx.doi.org/10.1210/me.2002-0074] [PMID: 12145346]
[19]
Miller, A.W.; Tulbert, C.; Puskar, M.; Busija, D.W. Enhanced endothelin activity prevents vasodilation to insulin in insulin resistance. Hypertension, 2002, 40(1), 78-82.
[http://dx.doi.org/10.1161/01.HYP.0000022806.87281.62] [PMID: 12105142]
[20]
De Ciuceis, C.; Rizzoni, D.; Porteri, E.; Boari, G.E.; Zani, F.; Miclini, M.; Tiberio, G.A.; Giulini, S.M.; Paiardi, S.; Rizzardi, N.; Platto, C.; Agabiti-Rosei, E. Effects of insulin on endothelial and contractile function of subcutaneous small resistance arteries of hypertensive and diabetic patients. J. Vasc. Res., 2008, 45(6), 512-520.
[http://dx.doi.org/10.1159/000128604] [PMID: 18451634]
[21]
Ltd, B. Bodystat 1500 user manual; , 2003.
[22]
WHO. Physical Status: The Use and Interpretation of Anthropometry Technical Report Series, 1995.
[23]
Wallace, T.M.; Levy, J.C.; Matthews, D.R. Use and abuse of HOMA modeling. Diabetes Care, 2004, 27(6), 1487-1495.
[http://dx.doi.org/10.2337/diacare.27.6.1487] [PMID: 15161807]
[24]
Banerjee, M.; Anderson, S.G.; Malik, R.A.; Austin, C.E.; Cruickshank, J.K. Small artery function 2 years postpartum in women with altered glycaemic distributions in their preceding pregnancy. Clin. Sci. (Lond.), 2012, 122(2), 53-61.
[http://dx.doi.org/10.1042/CS20110033] [PMID: 21745185]
[25]
Mulvany, M.J.; Aalkjaer, C. Structure and function of small arteries. Physiol. Rev., 1990, 70(4), 921-961.
[http://dx.doi.org/10.1152/physrev.1990.70.4.921] [PMID: 2217559]
[26]
Bund, S.J. Mechanical properties of small femoral arteries in spontaneously hypertensive rats. Clin. Exp. Hypertens., 1996, 18(8), 1013-1034.
[http://dx.doi.org/10.3109/10641969609081032] [PMID: 8922343]
[27]
Mulvany, M.J.; Halpern, W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ. Res., 1977, 41(1), 19-26.
[http://dx.doi.org/10.1161/01.RES.41.1.19] [PMID: 862138]
[28]
Imaeda, K.; Okayama, N.; Okouchi, M.; Omi, H.; Kato, T.; Akao, M.; Imai, S.; Uranishi, H.; Takeuchi, Y.; Ohara, H.; Fukutomi, T.; Joh, T.; Itoh, M. Effects of insulin on the acetylcholine-induced hyperpolarization in the guinea pig mesenteric arterioles. J. Diabetes Complications, 2004, 18(6), 356-362.
[http://dx.doi.org/10.1016/S1056-8727(03)00070-9] [PMID: 15531186]
[29]
McNally, P.G.; Lawrence, I.G.; Watt, P.A.; Hillier, C.; Burden, A.C.; Thurston, H. The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers. Diabetologia, 1995, 38(4), 467-473.
[http://dx.doi.org/10.1007/BF00410285] [PMID: 7796988]
[30]
Schinzari, F.; Tesauro, M.; Rovella, V.; Galli, A.; Mores, N.; Porzio, O.; Lauro, D.; Cardillo, C. Generalized impairment of vasodilator reactivity during hyperinsulinemia in patients with obesity-related metabolic syndrome. Am. J. Physiol. Endocrinol. Metab., 2010, 299(6), E947-E952.
[http://dx.doi.org/10.1152/ajpendo.00426.2010] [PMID: 20923961]
[31]
Taddei, S.; Virdis, A.; Mattei, P.; Natali, A.; Ferrannini, E.; Salvetti, A. Effect of insulin on acetylcholine-induced vasodilation in normotensive subjects and patients with essential hypertension. Circulation, 1995, 92(10), 2911-2918.
[http://dx.doi.org/10.1161/01.CIR.92.10.2911] [PMID: 7586259]
[32]
McNally, P.G.; Watt, P.A.; Rimmer, T.; Burden, A.C.; Hearnshaw, J.R.; Thurston, H. Impaired contraction and endothelium-dependent relaxation in isolated resistance vessels from patients with insulin-dependent diabetes mellitus. Clin. Sci. (Lond.), 1994, 87(1), 31-36.
[http://dx.doi.org/10.1042/cs0870031] [PMID: 8062516]
[33]
Muniyappa, R.; Sowers, J.R. Role of insulin resistance in endothelial dysfunction. Rev. Endocr. Metab. Disord., 2013, 14(1), 5-12.
[http://dx.doi.org/10.1007/s11154-012-9229-1] [PMID: 23306778]
[34]
Vehkavaara, S.; Yki-Järvinen, H. 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes. Arterioscler. Thromb. Vasc. Biol., 2004, 24(2), 325-330.
[http://dx.doi.org/10.1161/01.ATV.0000113817.48983.c5] [PMID: 14684428]
[35]
Schroeder, C.A., Jr; Chen, Y.L.; Messina, E.J. Inhibition of NO synthesis or endothelium removal reveals a vasoconstrictor effect of insulin on isolated arterioles. Am. J. Physiol., 1999, 276(3), H815-H820.
[PMID: 10070063]
[36]
Muniyappa, R.; Montagnani, M.; Koh, K.K.; Quon, M.J. Cardiovascular actions of insulin. Endocr. Rev., 2007, 28(5), 463-491.
[http://dx.doi.org/10.1210/er.2007-0006]
[37]
Symons, J.D.; McMillin, S.L.; Riehle, C.; Tanner, J.; Palionyte, M.; Hillas, E.; Jones, D.; Cooksey, R.C.; Birnbaum, M.J.; McClain, D.A.; Zhang, Q-J.; Gale, D.; Wilson, L.J.; Abel, E.D. Contribution of insulin and Akt1 signaling to endothelial nitric oxide synthase in the regulation of endothelial function and blood pressure. Circ. Res., 2009, 104(9), 1085-1094.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.189316] [PMID: 19342603]
[38]
Ouchi, N.; Ohishi, M.; Kihara, S.; Funahashi, T.; Nakamura, T.; Nagaretani, H.; Kumada, M.; Ohashi, K.; Okamoto, Y.; Nishizawa, H.; Kishida, K.; Maeda, N.; Nagasawa, A.; Kobayashi, H.; Hiraoka, H.; Komai, N.; Kaibe, M.; Rakugi, H.; Ogihara, T.; Matsuzawa, Y. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension, 2003, 42(3), 231-234.
[http://dx.doi.org/10.1161/01.HYP.0000083488.67550.B8] [PMID: 12860835]
[39]
Chen, H.; Montagnani, M.; Funahashi, T.; Shimomura, I.; Quon, M.J. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J. Biol. Chem., 2003, 278(45), 45021-45026.
[http://dx.doi.org/10.1074/jbc.M307878200] [PMID: 12944390]

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