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

Can J Cardiol. 2020 May;36(5):671-682. doi: 10.1016/j.cjca.2020.02.066. Epub 2020 Feb 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Hyperinsulinism / physiopathology*
  • Hypertension / physiopathology*
  • Insulin Resistance / physiology*
  • Kidney / metabolism
  • Leptin / blood
  • Metabolic Syndrome / physiopathology*
  • Obesity / physiopathology
  • Renin-Angiotensin System / physiology
  • Sodium / urine
  • Sympathetic Nervous System / physiology


  • Leptin
  • Sodium