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Decreased expression of Gi in erythrocytes from humans with type II diabetes is associated with impaired ATP release in response to decreased oxygen tension
Author(s) -
Hanson Madelyn,
Sprague Randy,
Bowles Elizabeth,
Achilleus David,
Stephenson Alan,
Ellsworth Mary
Publication year - 2008
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.22.1_supplement.1141.10
Subject(s) - chemistry , perfusion , endocrinology , medicine , biology
Erythrocytes (RBCs) release ATP in response to low O 2 tension (pO 2 ) via a signaling pathway that requires the G protein, Gi. RBC‐derived ATP is proposed to participate in the distribution of perfusion to meet tissue O 2 need. Here, we investigate the hypothesis that reduced Gi levels in RBCs, reported in humans with type II diabetes (DMII), is associated with impaired ATP release in response to reduced pO 2 . RBCs of rabbits, healthy humans (HH) and humans with DMII were placed in a tonometer and exposed to either 15% or 0% O 2 with 6% CO 2 (10 min). Reduced pO 2 induced ATP release from rabbit and HH RBCs of 93 ± 78% (n= 4, pO 2 =26 ± 2) and 292 ± 110% (n= 9, pO 2 = 18 ± 3), respectively. RBCs of humans with DMII failed to release ATP in response to this stimulus (n= 3, pO 2 = 24 ±1). To determine if RBCs that release ATP in response to reduced pO 2 have a role in determining vascular caliber, isolated perfused striated muscle arterioles were exposed to reduced pO 2 in the presence and absence of rabbit RBCs (15% hct). When rabbit RBCs were present, vessel diameter increased by 26 ± 11% (n= 7, pO 2 = 36 ± 5 mm Hg) while vessels perfused with buffer constricted (n= 10, pO 2 = 28 ± 3 mm Hg). These results demonstrate that decreased Gi levels in RBCs are associated with failure to release ATP in response to reduced pO 2 which could contribute to the vascular complications present in patients with DMII. Funded by AHA Fellowship, NIH grants HL‐64180, HL‐89094, ADA grant RA‐133.