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Canadian Journal of Cardiology

Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited

  • Alexandre A. da Silva
    Correspondence
    Corresponding author: Dr Alexandre A. da Silva, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, Mississippi 39216-4505, USA. Tel.: +1-601-984-1826; fax: +1-601-984-1833.
    Affiliations
    Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
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  • Jussara M. do Carmo
    Affiliations
    Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
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  • Xuan Li
    Affiliations
    Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
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  • Zhen Wang
    Affiliations
    Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
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  • Alan J. Mouton
    Affiliations
    Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
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  • John E. Hall
    Affiliations
    Department of Physiology and Biophysics, Mississippi Center for Obesity Research, and Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi, USA
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Published:February 11, 2020DOI:https://doi.org/10.1016/j.cjca.2020.02.066

      Abstract

      Hyperinsulinemia and insulin resistance were proposed more than 30 years ago to be important contributors to elevated blood pressure (BP) associated with obesity and the metabolic syndrome, also called syndrome X. Support for this concept initially came from clinical and population studies showing correlations among hyperinsulinemia, insulin resistance, and elevated BP in individuals with metabolic syndrome. Short-term studies in experimental animals and in humans provided additional evidence that hyperinsulinemia may evoke increases in sympathetic nervous system (SNS) activity and renal sodium retention that, if sustained, could increase BP. Although insulin infusions may increase SNS activity and modestly raise BP in rodents, chronic insulin administration does not significantly increase BP in lean or obese insulin-resistant rabbits, dogs, horses, or humans. Multiple studies in humans and experimental animals have also shown that severe insulin resistance and hyperinsulinemia may occur in the absence of elevated BP. These observations question whether insulin resistance and hyperinsulinemia are major factors linking obesity/metabolic syndrome with hypertension. Other mechanisms, such as physical compression of the kidneys, activation of the renin-angiotensin-aldosterone system, hyperleptinemia, stimulation of the brain melanocortin system, and SNS activation, appear to play a more critical role in initiating hypertension in obese subjects with metabolic syndrome. However, the metabolic effects of insulin resistance, including hyperglycemia and dyslipidemia, appear to interact synergistically with increased BP to cause vascular and kidney injury that can exacerbate the hypertension and associated injury to the kidneys and cardiovascular system.

      Résumé

      L'hyperinsulinémie et l'insulinorésistance ont été décrits il y a plus de 30 ans comme étant des facteurs importants contribuant à une pression artérielle (PA) élevée associée à l'obésité et au syndrome métabolique, également appelé syndrome X. Ce concept a été initialement soutenu par des études cliniques et démographiques montrant des corrélations entre l'hyperinsulinémie, l'insulinorésistance et une PA élevée chez les personnes atteintes du syndrome métabolique. Des études de court terme sur des animaux de laboratoire et chez l'Homme ont fourni des preuves supplémentaires que l'hyperinsulinémie peut provoquer une augmentation de l'activité du système nerveux sympathique (SNS) et de la rétention de sodium au niveau rénal qui, si elle est maintenue, pourrait augmenter la PA. Bien que les perfusions d'insuline puissent accroître l'activité du SNS et augmenter légèrement la PA chez les rongeurs, l'administration chronique d'insuline n'augmente pas significativement la PA chez les individus insulinorésistants maigres ou obèses, que ce soit chez les lapins, les chiens, les chevaux ou chez l’Homme. De multiples études chez l'Homme et les animaux de laboratoire ont également montré qu'une hyperinsulinémie et une insulinorésistance sévère peuvent survenir en absence de PA élevée. Ces observations amènent à se demander si l’insulinorésistance et l'hyperinsulinémie sont des facteurs majeurs liant l'obésité et le syndrome métabolique à l'hypertension. D'autres mécanismes, tels que la compression physique des reins, l'activation du système rénine-angiotensine-aldostérone, l'hyperleptinémie, la stimulation du système à mélanocortine du cerveau et l'activation du SNS, semblent jouer un rôle plus critique dans l'initiation de l'hypertension chez les sujets obèses atteints d'un syndrome métabolique. Cependant, les effets métaboliques de l'insulinorésistance, notamment l'hyperglycémie et la dyslipidémie, semblent interagir en synergie avec l'augmentation de la PA pour provoquer des lésions vasculaires et rénales qui peuvent exacerber l'hypertension et les dommages associés aux reins et au système cardiovasculaire.
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