(Circulation. 1997;96:4104-4113.)
© 1997 American Heart Association, Inc.
Articles |
Insulin as a Vascular and Sympathoexcitatory Hormone
Implications for Blood Pressure Regulation, Insulin Sensitivity, and Cardiovascular Morbidity
From the Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Correspondence to Dr Urs Scherrer, Department of Internal Medicine, BH 10.642, CHUV, CH-1011 Lausanne, Switzerland. E-mail Urs.Scherrer{at}chuv.hospvd.ch
Abstract The past several years have witnessed a major surge of interest in the cardiovascular actions of insulin. This interest has stemmed on the one hand from epidemiological studies that demonstrated an association between obesity, insulin resistance, and hypertension, leading to the so-called insulin hypothesis of hypertension. On the other hand, this interest has been stimulated by experimental evidence suggesting that the vascular actions of insulin may play a role in its main action, namely the promotion of glucose uptake in skeletal muscle tissue. Two tenets have emerged about how insulin may exert its cardiovascular actions. First, it is now firmly established that acute insulin administration stimulates sympathetic nerve activity in both animals and humans. Second, there is increasing evidence that insulin stimulates muscle blood flow, an effect that appears to be mediated at least in part by an endothelium-dependent mechanism. This review summarizes the current understanding and gaps in knowledge on cardiovascular actions of insulin in humans and pathophysiological consequences of derangements of such actions.
Key Words: insulin • nervous system, autonomic • nitric oxide • hypertension • vasodilation
This article has been cited by other articles:
 |
|
 |
|
  G. Grassi, G. Bolla, F. Quarti-Trevano, F. Arenare, G. Brambilla, and G. Mancia Sympathetic activation in congestive heart failure: Reproducibility of neuroadrenergic markers Eur J Heart Fail, December 1, 2008; 10(12): 1186 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. MacDonald, M. C. Petrie, N. M. Hawkins, J. R. Petrie, M. Fisher, R. McKelvie, D. Aguilar, H. Krum, and J. J.V. McMurray Diabetes, left ventricular systolic dysfunction, and chronic heart failure Eur. Heart J., May 2, 2008; 29(10): 1224 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Perciaccante Cardiovascular Autonomic Dysfunction as a Link Between Insulin Resistance and Nocturnal Blood Pressure Elevation Hypertension, April 1, 2008; 51(4): e30 - e30. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Muniyappa, M. Montagnani, K. K. Koh, and M. J. Quon Cardiovascular Actions of Insulin Endocr. Rev., August 1, 2007; 28(5): 463 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Kim, R. Krogh-Madsen, P. Rasmussen, P. Plomgaard, S. Ogoh, N. H. Secher, and J. J. van Lieshout Effects of hyperglycemia on the cerebrovascular response to rhythmic handgrip exercise Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H467 - H473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. B Patle, J. A De Lemos, K. L Wyne, and D. K McGuire Thiazolidinediones and risk for atherosclerosis: pleiotropic effects of PPAR{gamma} agonism Diabetes and Vascular Disease Research, September 1, 2006; 3(2): 65 - 71. [Abstract] [PDF]
|
|
|
|
 |
|
 P. Ruggeri, A. Brunori, C. E. Cogo, D. Storace, F. Di Nardo, and R. Burattini Enhanced sympathetic reactivity associates with insulin resistance in the young Zucker rat Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R376 - R382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Roberts and H. Gammill Insulin Resistance in Preeclampsia Hypertension, March 1, 2006; 47(3): 341 - 342. [Full Text] [PDF]
|
|
|
|
 |
|
 D. O'Donovan, C. Feinle-Bisset, C. Chong, A. Cameron, A. Tonkin, J. Wishart, M. Horowitz, and K. L. Jones Intraduodenal Guar Attenuates the Fall in Blood Pressure Induced by Glucose in Healthy Older Adults J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(7): 940 - 946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gentilcore, R. Visvanathan, A. Russo, R. Chaikomin, J. E. Stevens, J. M. Wishart, A. Tonkin, M. Horowitz, and K. L. Jones Role of nitric oxide mechanisms in gastric emptying of, and the blood pressure and glycemic responses to, oral glucose in healthy older subjects Am J Physiol Gastrointest Liver Physiol, June 1, 2005; 288(6): G1227 - G1232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patel, K. L Wyne, and D. K McGuire Thiazolidinediones, peripheral oedema and congestive heart failure: what is the evidence? Diabetes and Vascular Disease Research, May 1, 2005; 2(2): 61 - 66. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Porte Jr., D. G. Baskin, and M. W. Schwartz Insulin Signaling in the Central Nervous System: A Critical Role in Metabolic Homeostasis and Disease From C. elegans to Humans Diabetes, May 1, 2005; 54(5): 1264 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Hofman, F. Regan, W. E. Jackson, C. Jefferies, D. B. Knight, E. M. Robinson, and W. S. Cutfield Premature Birth and Later Insulin Resistance N. Engl. J. Med., November 18, 2004; 351(21): 2179 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cook, O. Hugli, M. Egli, B. Menard, S. Thalmann, C. Sartori, C. Perrin, P. Nicod, B. Thorens, P. Vollenweider, et al. Partial Gene Deletion of Endothelial Nitric Oxide Synthase Predisposes to Exaggerated High-Fat Diet--Induced Insulin Resistance and Arterial Hypertension Diabetes, August 1, 2004; 53(8): 2067 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Grossini, A. Battaglia, G. Bona, D. A. S. G. Mary, C. Molinari, and G. Vacca The effects of insulin on mesenteric blood flow in anaesthetized pigs Exp Physiol, July 1, 2004; 89(4): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rodriguez, T. R. Gaunt, S. D. O'Dell, X.-h. Chen, D. Gu, E. Hawe, G. J. Miller, S. E. Humphries, and I. N.M. Day Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits Hum. Mol. Genet., April 1, 2004; 13(7): 715 - 725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Laine, J Sundell, P Nuutila, O T Raitakari, M Luotolahti, T Ronnemaa, T Elomaa, P Koskinen, and J Knuuti Insulin induced increase in coronary flow reserve is abolished by dexamethasone in young men with uncomplicated type 1 diabetes Heart, March 1, 2004; 90(3): 270 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Harris and K. A. Matthews Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease Psychosom Med, March 1, 2004; 66(2): 153 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Grassi and G. Mancia Neurogenic Hypertension: Is the Enigma of Its Origin Near the Solution? Hypertension, February 1, 2004; 43(2): 154 - 155. [Full Text] [PDF]
|
|
|
|
|
|
U. Campia, G. Sullivan, M. B. Bryant, M. A. Waclawiw, M. J. Quon, and J. A. Panza Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H76 - H82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Huggett, E. M. Scott, S. G. Gilbey, J. B. Stoker, A. F. Mackintosh, and D. A.S.G. Mary Impact of Type 2 Diabetes Mellitus on Sympathetic Neural Mechanisms in Hypertension Circulation, December 23, 2003; 108(25): 3097 - 3101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.W.E. Sabelis, P.J. Senden, M.L. Zonderland, A. van de Wiel, J.P.M. Wielders, I.A. Huisveld, T.W. van Haeften, and W.L. Mosterd Determinants of insulin sensitivity in chronic heart failure Eur J Heart Fail, December 1, 2003; 5(6): 759 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vecchione, A. Aretini, A. Maffei, G. Marino, G. Selvetella, R. Poulet, V. Trimarco, G. Frati, and G. Lembo Cooperation Between Insulin and Leptin in the Modulation of Vascular Tone Hypertension, August 1, 2003; 42(2): 166 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. N. Kernan, S. E. Inzucchi, C. M. Viscoli, L. M. Brass, D. M. Bravata, and R. I. Horwitz Insulin resistance and risk for stroke Neurology, September 24, 2002; 59(6): 809 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Refsgaard, C. Thomsen, F. Andreasen, and O. Gotzsche Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure Eur J Heart Fail, August 1, 2002; 4(4): 445 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. GLICK Screening for traditional risk factors for cardiovascular disease: A review for oral health care providers J Am Dent Assoc, March 1, 2002; 133(3): 291 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Davy, C. L. Melby, S. D. Beske, R. C. Ho, L. R. Davrath, and K. P. Davy Oat Consumption Does Not Affect Resting Casual and Ambulatory 24-h Arterial Blood Pressure in Men with High-Normal Blood Pressure to Stage I Hypertension J. Nutr., March 1, 2002; 132(3): 394 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Westerbacka, A. Seppala-Lindroos, and H. Yki-Jarvinen Resistance to Acute Insulin Induced Decreases in Large Artery Stiffness Accompanies the Insulin Resistance Syndrome J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5262 - 5268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Russell III, D. Chyun, S. Song, R. S. Sherwin, W. V. Tamborlane, F. A. Lee, M. A. Pfeifer, F. Rife, F. J. T. Wackers, and L. H. Young Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients Am J Physiol Endocrinol Metab, November 1, 2001; 281(5): E1029 - E1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bohlooly-Y, L. Carlson, B. Olsson, H. Gustafsson, I. J. L. Andersson, J. Tornell, and G. Bergstrom Vascular Function and Blood Pressure in GH Transgenic Mice Endocrinology, August 1, 2001; 142(8): 3317 - 3323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Negrao, I. C. Trombetta, L. T. Batalha, M. M. Ribeiro, M. U. P. B. Rondon, T. Tinucci, C. L. M. Forjaz, A. C. P. Barretto, A. Halpern, and S. M. F. Villares Muscle metaboreflex control is diminished in normotensive obese women Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H469 - H475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Misurski, S.-Q. Wu, J. R. McNeill, T. W. Wilson, and V. Gopalakrishnan Insulin-Induced Biphasic Responses in Rat Mesenteric Vascular Bed : Role of Endothelin Hypertension, May 1, 2001; 37(5): 1298 - 1302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M Sharma and S. Engeli The renin-angiotensin system in obesity hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S114 - S119. [PDF]
|
|
|
|
|
|
K. Mather, M. Laakso, S. Edelman, G. Hook, and A. Baron Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1264 - E1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Grassi, G. Seravalle, R. Dell'Oro, C. Turri, G. B. Bolla, and G. Mancia Adrenergic and Reflex Abnormalities in Obesity-Related Hypertension Hypertension, October 1, 2000; 36(4): 538 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Capaldo, G. Lembo, V. Rendina, R. Guida, P. Marzullo, A. Colao, G. Lombardi, and L. Saccà Muscle Sympathetic Nerve Activity in Patients with Acromegaly J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3203 - 3207. [Abstract] [Full Text]
|
|
|
|
|
|
N Suskin, R.S McKelvie, R.J Burns, R Latini, D Pericak, J Probstfield, J.L Rouleau, C Sigouin, C.B Solymoss, R Tsuyuki, et al. Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure Eur. Heart J., August 2, 2000; 21(16): 1368 - 1375. [Abstract] [PDF]
|
|
|
|
|
|
A. Katz, S. S. Nambi, K. Mather, A. D. Baron, D. A. Follmann, G. Sullivan, and M. J. Quon Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2402 - 2410. [Abstract] [Full Text]
|
|
|
|
|
|
H. Laine, P. Nuutila, M. Luotolahti, C. Meyer, T. Elomaa, P. Koskinen, T. Rönnemaa, and J. Knuuti Insulin-Induced Increment of Coronary Flow Reserve Is Not Abolished by Dexamethasone in Healthy Young Men J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1868 - 1873. [Abstract] [Full Text]
|
|
|
|
|
|
K. Kuboki, Z. Y. Jiang, N. Takahara, S. W. Ha, M. Igarashi, T. Yamauchi, E. P. Feener, T. P. Herbert, C. J. Rhodes, and G. L. King Regulation of Endothelial Constitutive Nitric Oxide Synthase Gene Expression in Endothelial Cells and In Vivo : A Specific Vascular Action of Insulin Circulation, February 15, 2000; 101(6): 676 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Muntzel Insulin-mediated sympathoexcitation in obesity and type 2 diabetes Nephrol. Dial. Transplant., October 1, 1999; 14(10): 2282 - 2285. [Full Text] [PDF]
|
|
|
|
|
|
C. Sartori, L. Trueb, P. Nicod, and U. Scherrer Effects of Sympathectomy and Nitric Oxide Synthase Inhibition on Vascular Actions of Insulin in Humans Hypertension, October 1, 1999; 34(4): 586 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, S. S. Nambi, C. M. Kilcoyne, W. K. Choucair, A. Katz, M. J. Quon, and J. A. Panza Insulin Stimulates Both Endothelin and Nitric Oxide Activity in the Human Forearm Circulation, August 24, 1999; 100(8): 820 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Doenst, R. T. Richwine, M. S. Bray, G. W. Goodwin, O.H. Frazier, and H. Taegtmeyer Insulin improves functional and metabolic recovery of reperfused working rat heart Ann. Thorac. Surg., June 1, 1999; 67(6): 1682 - 1688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Daniels, J. A. Morrison, D. L. Sprecher, P. Khoury, and T. R. Kimball Association of Body Fat Distribution and Cardiovascular Risk Factors in Children and Adolescents Circulation, February 2, 1999; 99(4): 541 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Van De Borne, M. Hausberg, R. P. Hoffman, A. L. Mark, and E. A. Anderson Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R178 - R183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Russell III, R. Yin, M. J. Caplan, X. Hu, J. Ren, G. I. Shulman, A. J. Sinusas, and L. H. Young Additive Effects of Hyperinsulinemia and Ischemia on Myocardial GLUT1 and GLUT4 Translocation In Vivo Circulation, November 17, 1998; 98(20): 2180 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cardillo, C. M. Kilcoyne, S. S. Nambi, R. O. Cannon III, M. J. Quon, and J. A. Panza Vasodilator Response to Systemic But Not to Local Hyperinsulinemia in the Human Forearm Hypertension, October 1, 1998; 32(4): 740 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hasdai, R. A. Rizza, D. R. Holmes Jr, D. M. Richardson, P. Cohen, and A. Lerman Insulin and Insulin-like Growth Factor-I Cause Coronary Vasorelaxation In Vitro Hypertension, August 1, 1998; 32(2): 228 - 234. [Abstract] [Full Text] [PDF]
|
|