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Insulin Inhibits Low pO2‐Induced ATP Release from Human Erythrocytes (RBCs): Implications for Vascular Control in Pre‐Diabetes
Author(s) -
Hanson Madelyn,
Ellsworth Mary,
Achilleus David,
Bowles Elizabeth,
Stephenson Alan,
Adderley Shaquria,
Sridharan Meera,
Sprague Randy
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.948.15
Subject(s) - insulin , medicine , endocrinology , hyperinsulinemia , skeletal muscle , vasodilation , chemistry , diabetes mellitus , biology , insulin resistance
RBCs release ATP when exposed to low O 2 tension (pO 2 ). This ATP participates in the matching of O 2 supply with need in skeletal muscle by stimulating increases in blood flow to areas with increased O 2 demand. Here we investigate the hypothesis that hyperinsulinemia, as occurs in pre‐diabetes, inhibits ATP release from RBCs exposed to low pO 2 , impairing this cell's ability to stimulate vasodilation in response to reduced extraluminal pO 2 . RBCs were exposed to low O 2 (14 ± 1 mm Hg) in the absence and presence of insulin (1 nM). Insulin attenuated ATP release from 16 ± 4 to 8 ± 3 nmoles/4x10 8 RBCs (n=6, P <0.01). To determine a functional consequence of this action of insulin, we examined the ability of isolated skeletal muscle arterioles perfused with buffer containing RBCs to dilate in response to decreased extraluminal pO 2 (21 ± 4 mm Hg, n=10). In vessels perfused with untreated RBCs, low extraluminal pO 2 resulted in a 9 ± 3% increase in diameter ( P <0.05). In contrast, when RBCs were treated with insulin, the vessels failed to dilate in response to low pO 2 . These studies show that insulin inhibits ATP release from RBCs in response to reduced pO 2 and impairs their ability to stimulate dilation of skeletal muscle arterioles. These results suggest that the hyperinsulinemia of pre‐diabetes could hinder the matching of O 2 supply with need in skeletal muscle. Funded by AHA Fellowship (MH), ADA grant RA‐133, NIH grants HL‐64180 and HL‐89094.