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Erythrocytes (RBCs) of Humans and Rats with Type 2 Diabetes (DM2) Fail to Release ATP or Stimulate Dilation of Isolated Resistance Vessels in Response to Low Oxygen Tension
Author(s) -
Sprague Randy,
Hanson Madelyn,
Achilleus David,
Bowles Elizabeth,
Stephenson Alan,
Ellsworth Mary
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.1036.2
Subject(s) - skeletal muscle , chemistry , medicine , endocrinology , type 2 diabetes , contraction (grammar) , biology , diabetes mellitus
Low oxygen tension‐induced ATP release from RBCs contributes to the matching of O 2 supply with O 2 demand in skeletal muscle. RBCs of humans with DM2 failed to release ATP in response to pharmacological activation of the pathway for low O 2 ‐induced ATP release. We investigated the hypothesis that RBCs of humans and rats with DM2 (12 week Zucker Diabetic Fatty [ZDF] rats) would also fail to release ATP in response to low O 2 and would not stimulate dilation of isolated arterioles exposed to reduced extraluminal O 2 . RBCs of healthy humans (n=10) and ZDF controls (n=4) released significantly more ATP (230±68 and 654±197%, respectively) when exposed to low O 2 (19 ± 1 mm Hg) than did RBCs of both humans (n=6) and rats (n=3) with DM2 (56±29 and 64±4%, respectively) (P<0.05). To ascertain if there is a functional consequence of this failure to release ATP, we perfused isolated skeletal muscle arterioles with buffer containing RBCs and decreased the level of extraluminal O 2 . Vessels perfused with RBCs of healthy humans (n=3) increased their diameter by 20 ± 4% ( P <0.01) when PO 2 was decreased from 139 ± 5 to 16 ± 7 mm Hg. In contrast, when the buffer contained RBCs of humans with DM2, the increase was only 5.3% (n=2). These studies suggest that in DM2, ATP release from RBCs in response to reduced O 2 is impaired which would diminish the role of these cells as regulators of microvascular perfusion. (ADA grant RA‐133, NIH grants HL‐64180 and HL‐89094)