Divergent actions of chronic insulin treatment in vivo versus acute treatment ex vivo on diabetic-induced endothelial dysfunction

Life Sci. 1997;60(25):PL371-6. doi: 10.1016/s0024-3205(97)00292-0.


Streptozotocin-induced diabetes is associated with hyperglycemia and hypoinsulinemia. The role of insulin in diabetes-induced endothelial dysfunction is unknown. In the present study, we evaluated the effect of chronic insulin treatment in vivo versus acute insulin administration ex vivo on endothelium-dependent relaxation in aortic rings of the streptozotocin-induced diabetic rat. Relaxation to acetylcholine (but not A23187) was impaired in diabetic compared to control rings. This defect was prevented by chronic insulin treatment but was not reversed by acute insulin administration ex vivo. Thus, endothelial dysfunction in the streptozotocin-induced diabetic rat is specific for the chronic diabetic state and not to vascular toxicity of streptozotocin. Nevertheless, it is apparent that insulin at a physiological concentration does not cause an acute direct effect on facilitating endothelium-dependent relaxation in diabetic blood vessels.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Blood Glucose / drug effects
  • Culture Media
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / physiopathology*
  • Drug Administration Schedule
  • Endothelium, Vascular / physiopathology*
  • Hypoglycemic Agents / administration & dosage*
  • Insulin / administration & dosage*
  • Male
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology
  • Norepinephrine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Diseases / etiology*
  • Vascular Diseases / prevention & control*


  • Adrenergic alpha-Agonists
  • Blood Glucose
  • Culture Media
  • Hypoglycemic Agents
  • Insulin
  • Norepinephrine