Insulin inhibits low oxygen-induced ATP release from human erythrocytes: implication for vascular control.
OBJECTIVE
ATP released from human erythrocytes in response to reduced oxygen tension (pO(2)) participates in the matching of oxygen (O(2)) supply with need in skeletal muscle by stimulating increases in blood flow to areas with increased O(2) demand. Here, we investigated the hypothesis that hyperinsulinemia inhibits ATP release from erythrocytes and impairs their ability to stimulate dilation of isolated arterioles exposed to decreased extraluminal pO(2).


METHODS
Erythrocyte ATP release was stimulated pharmacologically (mastoparan 7) and physiologically (reduced pO(2)) in the absence or presence of insulin. We also examined the ability of isolated skeletal muscle arterioles perfused with buffer containing erythrocytes treated with insulin or its vehicle (saline) to dilate in response to decreased extraluminal pO(2).


RESULTS
Insulin significantly attenuated mastoparan 7- and reduced pO(2)-induced ATP release. In vessels perfused with untreated erythrocytes, low extraluminal pO(2) resulted in an increase in vessel diameter. In contrast, when erythrocytes were treated with insulin, no vasodilation occurred.


CONCLUSIONS
These studies demonstrate that insulin inhibits ATP release from erythrocytes in response to reduced pO(2) and impairs their ability to stimulate dilation of skeletal muscle arterioles. These results suggest that hyperinsulinemia could hinder the matching of O(2) supply with need in skeletal muscle.
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA. stumpfms@slu.edu
Madelyn S
MS
Hanson
Mary L
ML
Ellsworth
David
D
Achilleus
Alan H
AH
Stephenson
Elizabeth A
EA
Bowles
Meera
M
Sridharan
Shaquria
S
Adderley
Randy S
RS
Sprague
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001783:Blood Flow Velocity / Q000187:drug effects; D006224:Cricetinae; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply; D010100:Oxygen / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; C084070:Mas7 protein, synthetic; D010455:Peptides; D000255:Adenosine Triphosphate; D010100:Oxygen