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Insulin Resistance and Hypertension

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Endocrine Hypertension

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

IR has been reported to be associated with elevated blood pressure and hypertension. It is reasonable to postulate that IR is causally related to increased rates of hypertension in IR, especially considering abnormalities in SNS activity, renal salt handling, and endothelial function. Other, albeit indirect, evidence for the causal role of IR in blood pressure elevation comes from studies where improvement in IR resulted in lowering of blood pressure. A likely mechanistic explanation for the association between IR and blood pressure is that adipocyte dysfunction, elevated free fatty acid levels and elevated insulin levels, over time, may adversely affect systems involved in blood pressure regulation. Since the association between IR and elevated blood pressure is not found in all populations, these studies also suggest that, depending on genetic and environmental factors, these IR-induced changes lead eventually to increased blood pressure, or diabetes, or cardiovascular disease, or any combination of these. Of these, the time-dependent effects on blood pressure, even if not detectable in all individuals as a measurable change, may be particularly significant from a population perspective. Importantly, improvement in IR will likely have significant overall beneficial effects, to prevent or postpone the development of diabetes, hypertension, and cardiovascular disease.

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References

  1. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214–23.

    PubMed  CAS  Google Scholar 

  2. Caumo A, Bergman RN, Cobelli C. Insulin sensitivity from meal tolerance tests in normal subjects: a minimal model index. J Clin Endocrinol Metab. 2000;85(11):4396–402.

    Article  PubMed  CAS  Google Scholar 

  3. Pillonetto G, Caumo A, Cobelli C. Dynamic insulin sensitivity index: importance in diabetes. Am J Physiol Endocrinol Metab. 2010;298(3):E440–8.

    Article  PubMed  CAS  Google Scholar 

  4. Bergman RN. Minimal model: perspective from 2005. Horm Res. 2005;64 Suppl 3:8–15.

    Article  PubMed  CAS  Google Scholar 

  5. Muscelli E, et al. Autonomic and hemodynamic responses to insulin in lean and obese humans. J Clin Endocrinol Metab. 1998;83(6):2084–90.

    Article  PubMed  CAS  Google Scholar 

  6. Steinberg HO, et al. Type II diabetes abrogates sex differences in endothelial function in premenopausal women. Circulation. 2000;101(17):2040–6.

    Article  PubMed  CAS  Google Scholar 

  7. Nuutila P, et al. Gender and insulin sensitivity in the heart and in skeletal muscles. Studies using positron emission tomography. Diabetes. 1995;44(1):31–6.

    Article  PubMed  CAS  Google Scholar 

  8. Saad MF, et al. Insulin and hypertension. Relationship to obesity and glucose intolerance in Pima Indians. Diabetes. 1990;39(11):1430–5.

    Article  PubMed  CAS  Google Scholar 

  9. Ferrannini E, et al. Insulin resistance, insulin response, and obesity as indicators of metabolic risk. J Clin Endocrinol Metab. 2007;92(8):2885–92.

    Article  PubMed  CAS  Google Scholar 

  10. Grassi G, et al. Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives. J Hypertens. 2004;22(12):2363–9.

    Article  PubMed  CAS  Google Scholar 

  11. Huggett RJ, et al. Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension. 2004;44(6):847–52.

    Article  PubMed  CAS  Google Scholar 

  12. Florian JP, Pawelczyk JA. Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans. Clin Sci (Lond). 2010;118(1):61–9.

    Article  CAS  Google Scholar 

  13. Quilliot D, et al. Impaired autonomic control of heart rate and blood pressure in obesity: role of age and of insulin-resistance. Clin Auton Res. 2001;11(2):79–86.

    Article  PubMed  CAS  Google Scholar 

  14. Valensi P, et al. Influence of parasympathetic dysfunction and hyperinsulinemia on the hemodynamic response to an isometric exercise in non-insulin-dependent diabetic patients. Metabolism. 1998;47(8):934–9.

    Article  PubMed  CAS  Google Scholar 

  15. Guyton AC. Roles of the kidneys and fluid volumes in arterial pressure regulation and hypertension. Chin J Physiol. 1989;32(2):49–57.

    PubMed  CAS  Google Scholar 

  16. Charra B, Chazot C. Volume control, blood pressure and cardiovascular function. Lessons from hemodialysis treatment. Nephron Physiol. 2003;93(4):94–101.

    Article  Google Scholar 

  17. Hall JE. Renal function in one-kidney, one-clip hypertension and low renin essential hypertension. Am J Hypertens. 1991;4(10 Pt 2):523S–33.

    PubMed  CAS  Google Scholar 

  18. Hall JE. Mechanisms of abnormal renal sodium handling in obesity hypertension. Am J Hypertens. 1997;10(5 Pt 2):49S–55.

    Article  PubMed  CAS  Google Scholar 

  19. Strazzullo P, et al. Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study. J Hypertens. 2006;24(8):1633–9.

    Article  PubMed  CAS  Google Scholar 

  20. Chen J, et al. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet. 2009;373(9666):829–35.

    Article  PubMed  CAS  Google Scholar 

  21. Hoffmann IS, Cubeddu LX. Increased blood pressure reactivity to dietary salt in patients with the metabolic syndrome. J Hum Hypertens. 2007;21(6):438–44.

    PubMed  CAS  Google Scholar 

  22. Steinberg HO, et al. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996;97(11):2601–10.

    Article  PubMed  CAS  Google Scholar 

  23. Sowers JR. Effects of insulin and IGF-I on vascular smooth muscle glucose and cation metabolism. Diabetes. 1996;45 Suppl 3:S47–51.

    PubMed  CAS  Google Scholar 

  24. Du X, et al. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest. 2006;116(4):1071–80.

    Article  PubMed  CAS  Google Scholar 

  25. Okon EB, et al. Compromised arterial function in human type 2 diabetic patients. Diabetes. 2005;54(8):2415–23.

    Article  PubMed  CAS  Google Scholar 

  26. Symons JD, et al. 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):1085–94.

    Article  PubMed  CAS  Google Scholar 

  27. Perticone F, et al. Endothelial dysfunction, ADMA and insulin resistance in essential hypertension. Int J Cardiol. 2010;142(3):236–41.

    Article  PubMed  Google Scholar 

  28. Sydow K, Mondon CE, Cooke JP. Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. Vasc Med. 2005;10 Suppl 1:S35–43.

    Article  PubMed  Google Scholar 

  29. Galipeau D, et al. Chronic thromboxane synthase inhibition prevents fructose-induced hypertension. Hypertension. 2001;38(4):872–6.

    PubMed  CAS  Google Scholar 

  30. Ferri C, et al. Plasma endothelin-1 levels in obese hypertensive and normotensive men. Diabetes. 1995;44(4):431–6.

    Article  PubMed  CAS  Google Scholar 

  31. Piatti PM, et al. Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome. Metabolism. 2000;49(6):748–52.

    Article  PubMed  CAS  Google Scholar 

  32. Irving RJ, et al. Activation of the endothelin system in insulin resistance. QJM. 2001;94(6):321–6.

    Article  PubMed  CAS  Google Scholar 

  33. Ferri C, De Mattia G. The effect of insulin on endothelin-1 (ET-1) secretion in human cultured endothelial cell. Metabolism. 1995;44(5):689–90.

    Article  PubMed  CAS  Google Scholar 

  34. Cardillo C, et al. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation. 1999;100(8):820–5.

    Article  PubMed  CAS  Google Scholar 

  35. Fernandez M, et al. Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care. 2008;31(1):121–7.

    Article  PubMed  CAS  Google Scholar 

  36. Anderson EA, et al. Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans. Hypertension. 1992;19(6 Pt 2):621–7.

    Article  PubMed  CAS  Google Scholar 

  37. Anderson EA, et al. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 1991;87(6):2246–52.

    Article  PubMed  CAS  Google Scholar 

  38. Laitinen T, et al. Effects of euglycaemic and hypoglycaemic hyperinsulinaemia on sympathetic and parasympathetic regulation of haemodynamics in healthy subjects. Clin Sci (Lond). 2003;105(3):315–22.

    Article  CAS  Google Scholar 

  39. Fugmann A, et al. Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal. Clin Sci (Lond). 2003;105(6):715–21.

    Article  CAS  Google Scholar 

  40. Baron AD, et al. Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure. Hypertension. 1993;21(2):129–35.

    Article  PubMed  CAS  Google Scholar 

  41. ter Maaten JC, et al. Relationship between insulin’s haemodynamic effects and insulin-­mediated glucose uptake. Eur J Clin Invest. 1998;28(4):279–84.

    Article  PubMed  Google Scholar 

  42. Buchanan TA, et al. Angiotensin II increases glucose utilization during acute hyperinsulinemia via a hemodynamic mechanism. J Clin Invest. 1993;92(2):720–6.

    Article  PubMed  CAS  Google Scholar 

  43. Baron AD, Brechtel G. Insulin differentially regulates systemic and skeletal muscle vascular resistance. Am J Physiol. 1993;265(1 Pt 1):E61–7.

    PubMed  CAS  Google Scholar 

  44. Laakso M, et al. Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity. Diabetes. 1990;39(8):965–74.

    Article  PubMed  CAS  Google Scholar 

  45. Steinberg HO, et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest. 1997;100(5):1230–9.

    Article  PubMed  CAS  Google Scholar 

  46. Liu J, et al. Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans. J Clin Endocrinol Metab. 2011;96:438–46.

    Article  PubMed  CAS  Google Scholar 

  47. Mittermayer F, et al. Rosiglitazone prevents free fatty acid-induced vascular endothelial ­dysfunction. J Clin Endocrinol Metab. 2007;92(7):2574–80.

    Article  PubMed  CAS  Google Scholar 

  48. Galletti F, et al. High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study. J Clin Endocrinol Metab. 2008;93(10):3922–6.

    Article  PubMed  CAS  Google Scholar 

  49. Li HY, et al. The negative correlation between plasma adiponectin and blood pressure depends on obesity: a family-based association study in SAPPHIRe. Am J Hypertens. 2008;21(4):471–6.

    Article  PubMed  CAS  Google Scholar 

  50. Steinberg HO, et al. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94(3):1172–9.

    Article  PubMed  CAS  Google Scholar 

  51. Eid HM, et al. Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia. Metabolism. 2007;56(4):464–9.

    Article  PubMed  CAS  Google Scholar 

  52. Baron AD, et al. Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men. J Clin Invest. 1994;93(6):2453–62.

    Article  PubMed  CAS  Google Scholar 

  53. Lembo G, et al. Insulin reduces reflex forearm sympathetic vasoconstriction in healthy humans. Hypertension. 1993;21(6 Pt 2):1015–9.

    Article  PubMed  CAS  Google Scholar 

  54. Fujishima S, et al. Effects of intra-arterial infusion of insulin on forearm vasoreactivity in hypertensive humans. Hypertens Res. 1995;18(3):227–33.

    Article  PubMed  CAS  Google Scholar 

  55. Huvers FC, et al. The enhanced pressor response in type 2 diabetes is not based upon a generalized increase in vascular responsiveness. Cardiovasc Res. 1998;38(1):206–14.

    Article  PubMed  CAS  Google Scholar 

  56. Su HY, et al. Effect of weight loss on blood pressure and insulin resistance in normotensive and hypertensive obese individuals. Am J Hypertens. 1995;8(11):1067–71.

    Article  PubMed  CAS  Google Scholar 

  57. Tiikkainen M, et al. Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women. Am J Clin Nutr. 2004;79(1):22–30.

    PubMed  CAS  Google Scholar 

  58. Dengel DR, et al. The independent and combined effects of weight loss and aerobic exercise on blood pressure and oral glucose tolerance in older men. Am J Hypertens. 1998;11(12):1405–12.

    Article  PubMed  CAS  Google Scholar 

  59. Basu A, et al. Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes. Diabetes Care. 2006;29(3):510–4.

    Article  PubMed  CAS  Google Scholar 

  60. Yosefy C, et al. Rosiglitazone improves, while Glibenclamide worsens blood pressure control in treated hypertensive diabetic and dyslipidemic subjects via modulation of insulin resistance and sympathetic activity. J Cardiovasc Pharmacol. 2004;44(2):215–22.

    Article  PubMed  CAS  Google Scholar 

  61. Paradisi G, et al. Troglitazone therapy improves endothelial function to near normal levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(2):576–80.

    Article  PubMed  CAS  Google Scholar 

  62. Rask E, et al. Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men. Diabetes Care. 2001;24(9):1640–5.

    Article  PubMed  CAS  Google Scholar 

  63. Muscelli E, et al. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes. 2008;57(5):1340–8.

    Article  PubMed  CAS  Google Scholar 

  64. Nauck MA. Unraveling the science of incretin biology. Eur J Intern Med. 2009;20 Suppl 2:S303–8.

    Article  PubMed  CAS  Google Scholar 

  65. Ban K, et al. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008;117(18):2340–50.

    Article  PubMed  CAS  Google Scholar 

  66. Yamamoto H, et al. Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons. J Clin Investig. 2002;110(1):43–52.

    PubMed  CAS  Google Scholar 

  67. Trapp S, Hisadome K. Glucagon-like peptide 1 and the brain: central actions-central sources? Auton Neurosci. 2011;161(1–2):14–9.

    Article  PubMed  CAS  Google Scholar 

  68. Hirata K, et al. Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model. Biochem Biophys Res Commun. 2009;380(1):44–9.

    Article  PubMed  CAS  Google Scholar 

  69. Nystrom T, et al. Glucagon-like peptide-1 relaxes rat conduit arteries via an endothelium-independent mechanism. Regul Pep. 2005;125(1–3):173–7.

    Article  Google Scholar 

  70. Gaspari T, et al. A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE−/− mouse model. Diab Vasc Dis Res. 2011;8(2):117–24.

    Article  PubMed  Google Scholar 

  71. Perez-Tilve D, et al. Exendin-4 increases blood glucose levels acutely in rats by activation of the sympathetic nervous system. Am J Physiol. 2010;298(5):E1088–96.

    CAS  Google Scholar 

  72. Liu Q, et al. The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats. Cardiovasc Diabetol. 2010;9:32.

    Article  PubMed  Google Scholar 

  73. Gardiner SM, et al. Possible involvement of GLP-1(9–36) in the regional haemodynamic effects of GLP-1(7–36) in conscious rats. Br J Pharmacol. 2010;161(1):92–102.

    Article  PubMed  CAS  Google Scholar 

  74. Nystrom T, et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol. 2004;287(6):E1209–15.

    Google Scholar 

  75. Gutzwiller JP, et al. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab. 2004;89(6):3055–61.

    Article  PubMed  CAS  Google Scholar 

  76. Bharucha AE, et al. Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans. American J Physiol Regul Integr Comp Physiol. 2008;295(3):R874–80.

    Article  CAS  Google Scholar 

  77. Halbirk M, et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol. 2010;298(3):H1096–102.

    CAS  Google Scholar 

  78. Okerson T, et al. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010;23(3):334–9.

    Article  PubMed  CAS  Google Scholar 

  79. Sjoholm A. Impact of glucagon-like peptide-1 on endothelial function. Diabetes Obes Metab. 2009;11 Suppl 3:19–25.

    Article  PubMed  Google Scholar 

  80. Ferrannini E, et al. Insulin resistance, hyperinsulinemia, and blood pressure: role of age and obesity. European Group for the Study of Insulin Resistance (EGIR). Hypertension. 1997;30(5):1144–9.

    Article  PubMed  CAS  Google Scholar 

  81. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991;14(3):173–94.

    Article  PubMed  CAS  Google Scholar 

  82. Pinkney JH, et al. Insulin resistance, insulin, proinsulin, and ambulatory blood pressure in type II diabetes. Hypertension. 1994;24(3):362–7.

    Article  PubMed  CAS  Google Scholar 

  83. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Experimental Medicine, Merck Research Laboratories, Rahway, NJ, USA

    Sudha S. Shankar

  2. Department of Diabetes and Endocrinology, Merck Research Laboratories, Rahway, NJ, USA

    Helmut O. Steinberg

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  1. Sudha S. Shankar
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  2. Helmut O. Steinberg
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Correspondence to Helmut O. Steinberg .

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Editors and Affiliations

  1. Dept. Medicine, Div. Endocrinology, Diabetes &, University of Mississippi Medical Center, N. State Street 2500, Jackson, 39216, Mississippi, USA

    Christian A Koch

  2. UNESCO Chair on Adolescent Health Care, Division of Endocrinology, University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, 11527, Greece

    George P Chrousos

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Shankar, S.S., Steinberg, H.O. (2013). Insulin Resistance and Hypertension. In: Koch, C., Chrousos, G. (eds) Endocrine Hypertension. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-548-4_12

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  • DOI: https://doi.org/10.1007/978-1-60761-548-4_12

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