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Deletion of PTP1B Corrects Obesity‐Induced Mesenteric Endothelial Dysfunction
Author(s) -
Ali Mohammed Irfan,
Mintz James D.,
Marrero Mario B.,
Stepp David W.
Publication year - 2007
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.21.6.a843-d
Subject(s) - endocrinology , medicine , dilator , insulin resistance , endothelial dysfunction , knockout mouse , leptin , insulin , acetylcholine , chemistry , obesity , mesenteric arteries , metabolic syndrome , sma* , receptor , artery , mathematics , combinatorics
Obesity has been linked to endothelial dysfunction (ED) in humans. Obese mice show ED, but the mechanisms of this are unknown. We hypothesized that insulin resistance is the underlying mechanism responsible for obesity‐induced ED. Obese Leptin receptor knockout mice (KH, n=12) and insulin sensitive Protein Tyrosine Phosphotase‐1B knockout (HK, n=9) mice were bred to make insulin sensitive obese dual knockout mice (KK, n=7). Lean mice (HH, n=14) were used as a control. Small mesenteric arteries (SMA, 25–150 μm) were mounted in vitro, pressurized (60 mmHg) and ED was assessed by acetylcholine‐induced dilation (Ach, 10 −8 –10 −3 M). Passive mechanics were assessed in Ø‐Ca 2+ ‐Krebs solution over 40–120 mmHg. HbA1C was increased in KH vs. HH (10.0±.1% vs. 5.0±.1%, p<0.05) but reduced in KK vs. KH (7.0±.4% vs. 10±.7%, p<0.05). KH were much less reactive to Ach than HH (max=50±4% vs. 70±3%, p<0.05). HK had a similar Ach response to HH (71±2% vs. 70±3%). KK reduced the ED shown in KH (64±4% vs. 50±4%, p<0.05). Passive mechanics were similar in all groups, thus ruling out structural changes as a reason for KH dilator deficits. We conclude that obesity induces ED in SMA secondary to insulin resistance. NIH,HL76533