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Obesity induced‐insulin resistance causes endothelial dysfunction without reducing the vascular response to hindlimb ischemia.
Author(s) -
Belin de Chantemele Eric J,
Ali Mohammed Irfan,
Mintz James,
Stepp David W
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.592.3
Subject(s) - medicine , hindlimb , ischemia , endocrinology , insulin resistance , endothelial dysfunction , diabetes mellitus , obesity
Type II diabetes (T2DM) impairs vascular growth but the progression and mechanisms are poorly understood. To determine whether obesity and early T2DM impair endothelium‐dependent relaxation and vascular response to ischemia, acetylcholine‐induced dilatation and angiogenic response to ischemia were assessed in young (C57) and old lean mice (old C57), in obese (db‐C57), and in mice suffering an early (db‐KsJ) and sustained T2DM (old db‐KsJ). Glycemia gradually increases from the db‐C57 to the old db‐KsJ while early and established T2DM significantly reduced the level of insulin which was significantly increased in the 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 and angiography. Aging (‐21%), obesity (‐45%), early (‐58%) and sustained T2DM (‐69%) induced a progressive impairment of the endothelium‐dependent relaxation of the gracilis artery. Early and sustained T2DM only, impaired skin blood flow recovery. Impairment of the vascular collateralization was observed in the old db‐KsJ only. These results demonstrate that endothelial dysfunction induced by aging and obesity is insufficient to alter the angiogenic response to ischemia. Furthermore the development of frank T2DM is required to impair the vascular response to hindlimb ischemia.