Exogenous endothelin-1 causes peripheral insulin resistance in healthy humans

Acta Physiol Scand. 1997 Oct;161(2):211-20. doi: 10.1046/j.1365-201X.1997.00212.x.


In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg-1 min-1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 +/- 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 +/- 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 +/- 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 +/- 6% (P < 0.001) and 20 +/- 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Electrolytes / blood
  • Endothelin-1 / administration & dosage
  • Endothelin-1 / blood
  • Endothelin-1 / pharmacology*
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Hemodynamics / drug effects
  • Humans
  • Infusions, Intravenous
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Liver Circulation / drug effects
  • Liver Circulation / physiology
  • Liver Function Tests
  • Male


  • Blood Glucose
  • Electrolytes
  • Endothelin-1
  • Insulin
  • Glucose