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Influence of obesity on insulin‐mediated dilation in the human microcirculation
Author(s) -
Borbouse Lena,
Gutterman David D.
Publication year - 2012
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.26.1_supplement.866.2
Subject(s) - insulin , medicine , endocrinology , adipose tissue , vasodilation , obesity , dilation (metric space) , mathematics , combinatorics
Obesity is known to reduce both insulin sensitivity to glucose and endothelial‐derived NO‐dependent vasorelaxation to insulin, but little is known about the effect of obesity on insulin‐induced dilation mediated by endothelial‐derived hyperpolarizing factors (EDHFs). We examined the influence of obesity on insulin‐mediated dilation in human adipose arterioles. Vasodilation in microvessels from human adipose tissue were examined in response to physiological concentrations of insulin (0.3 – 100 ng/ml) using videomicroscopy. Endothelial denudation or treatment with high K + (45 mM) abolished dilation to insulin in obese subjects, indicating an EDHF mechanism. Treatment with PEG‐catalase reduced insulin dilation in arterioles from lean (BMI 22.5 ± 1.1; m ± SE) and obese (BMI 31.0 ± 1.0) subjects by 47% and 45% respectively. In the presence of L‐NAME and indomethacin (INDO), PEG‐catalase abolished the remaining dilation to insulin in arterioles of lean subjects; but had no further effect in obese subjects. The mono‐oxygenase inhibitor MS‐PPOH had no effect on insulin dilation in obese subjects. We conclude that H 2 O 2 contributes significantly to EDHF dilation to insulin in lean subjects, but obesity induces a mechanistic switch to a non‐H 2 O 2 , non‐epoxyeicosatrienoic acid EDHF. (Supported by NHLBI grants HL‐094971 and HL‐080704 (DDG) and AHA Midwest Postdoctoral Fellowship Award).