Obesity induced-insulin resistance causes endothelial dysfunction without reducing the vascular response to hindlimb ischemia

Eric J. Belin de Chantemèle, M. Irfan Ali, James Mintz, David W. Stepp

Research output: Contribution to journalArticle

16 Scopus citations


Impairment of vascular growth is a hallmark of diabetic complications, but the progression and mechanisms are poorly understood. To determine whether obesity and early diabetes impair endothelium-dependent vasodilatation and vascular response to ischemia, microvascular function as well as angiogenic responses to ischemia were assessed in young (C57) and 6-month-old lean mice (old C57), in obese (db-C57) mice, and in mice suffering an early (db-KsJ) and sustained type 2 diabetes (old db-KsJ). Glycemia gradually increased from the db-C57 to the old db-KsJ. Early and established type II diabetes significantly reduced the level of insulin that was significantly increased in obese mice. Endothelial function was assessed in isolated resistance arteries while the angiogenic response induced by unilateral hindlimb ischemia was analyzed, after 28 days, with a laser Doppler flowmeter and angiography. Aging (-21%), obesity (-45%), as well as early (-58%) and sustained type II diabetes (-69%) induced a progressive impairment of the endothelium-dependent relaxation of the gracilis artery. Laser Doppler measurements demonstrated that only early and sustained type II diabetes impaired skin blood flow recovery. Vascular collateralization was reduced with aging and severely impaired in older db-KsJ mice, the two strains of mice in which ischemia reduced eNOS expression. These results demonstrate that endothelial dysfunction induced by obesity is insufficient to alter the angiogenic response to ischemia. Furthermore, the development of frank type II diabetes or increasing age is required to impair the vascular response to hindlimb ischemia. We conclude that additional risk factors or severe endothelial dysfunction may be requisite to impede the angiogenic response to ischemia.

Original languageEnglish (US)
Pages (from-to)707-717
Number of pages11
JournalBasic Research in Cardiology
Issue number6
Publication statusPublished - Jun 23 2009



  • Angiogenesis
  • Endothelium
  • Obesity
  • Type 2 diabetes
  • eNOS

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this