2006
DOI: 10.2337/db06-0555
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Reduced Expression of Gi in Erythrocytes of Humans With Type 2 Diabetes Is Associated With Impairment of Both cAMP Generation and ATP Release

Abstract: Human erythrocytes, by virtue of their ability to release ATP in response to physiological stimuli, have been proposed to participate in the regulation of local blood flow. A signal transduction pathway that relates these stimuli to ATP release has been described and includes the heterotrimeric G protein G i and adenylyl cyclase (AC). In this cell, G i activation results in increases in cAMP and, ultimately, ATP release. It has been reported that G i expression is decreased in animal models of diabetes and in … Show more

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Cited by 94 publications
(127 citation statements)
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“…As shown in Figure 7A, diamide caused the anticipated dose-dependent rise in band 3 tyrosine phosphorylation (lanes [1][2][3][4][5] and, similar to o-vanadate treatment, also promoted an analogous increase in the extractability of band 3 by Triton X-100 ( Figure 7B lanes 1-5). Diamide treatment in the presence of p72 Syk inhibitors led to an essentially complete abrogation of both band 3 phosphorylation and extractability without altering diamide's effect on band 3 oxidation ( Figure 7A-B lanes 6-10).…”
Section: Org Frommentioning
confidence: 92%
See 1 more Smart Citation
“…As shown in Figure 7A, diamide caused the anticipated dose-dependent rise in band 3 tyrosine phosphorylation (lanes [1][2][3][4][5] and, similar to o-vanadate treatment, also promoted an analogous increase in the extractability of band 3 by Triton X-100 ( Figure 7B lanes 1-5). Diamide treatment in the presence of p72 Syk inhibitors led to an essentially complete abrogation of both band 3 phosphorylation and extractability without altering diamide's effect on band 3 oxidation ( Figure 7A-B lanes 6-10).…”
Section: Org Frommentioning
confidence: 92%
“…Classic hormones/signaling molecules such as prostaglandin E 2 , insulin, epinephrine, endothelin, ADP, and NO are now known to modulate erythrocyte properties in an adaptive manner, and the functional activities of many intracellular signaling intermediates have been demonstrated to regulate erythrocyte behavior. [1][2][3][4][5] One of the major targets of erythrocyte signaling appears to be the predominant membrane-spanning protein, band 3. Band 3 (AE1) catalyzes the exchange of anions (primarily HCO 3 Ϫ for Cl Ϫ ) across the erythrocyte membrane, 6 anchors the spectrin/ actin cytoskeleton to the lipid bilayer, 7 organizes and regulates a complex of glycolytic enzymes, 8,9 participates in control of erythrocyte lifespan, 10,11 nucleates several important membrane-spanning proteins, 12 and serves as a docking site for multiple peripheral membrane proteins, including protein 4.1, protein 4.2, and several kinases and phosphatases.…”
Section: Introductionmentioning
confidence: 99%
“…This is potentially very important because it is known that some patient groups known to have low NO production or complications involving blood flow are also known to have RBCs that release lower than normal amounts of ATP upon pharmacological activation or physical deformation of the erythrocyte. Patients with primary pulmonary hypertension, 12 cystic fibrosis, 13 and diabetes 14,15 are example patient groups with these lower ATP release values. Figure 1 demonstrate that platelet NO can be measured via fluorescence spectrophotometry in tubing having a diameter that approximates an arteriole in vivo.…”
Section: Resultsmentioning
confidence: 99%
“…These results thus render the RBC a possible determinant of platelet physiology in vivo because it has been shown that the RBC is capable of releasing ATP via either mechanical deformation 9,14,16 or pharmacologically. 15 To demonstrate the ability of certain pharmaceuticals to increase the amount of ATP released from RBCs that are subjected to deformation, aliquots of a 7% hematocrit of RBCs were pumped through a 30-cm section of the microbore tubing having an inside diameter of 50 µm in the presence and absence of pentoxyfilline or iloprost. Pentoxyfilline is thought to improve blood flow via its ability to make the RBC more deformable through a radical scavenging mechanism.…”
Section: Resultsmentioning
confidence: 99%
“…RBC Na-Li and Na-H countertrans port activity was found to predict susceptibility to diabetes and hypertension [77,78]. Among many examples, Sprague et al, assessing protein expres sion levels by western blot analysis, reported that the expression of the heterotrimeric Gprotein G i is selectively decreased in RBCs of Type 2 diabe tes patients [79]. Antonelou et al identified secre tory CLU (sCLU), a chaperone that has been implicated in several pathological conditions, as a component attached to human RBCs [80].…”
Section: Rbc Membrane Proteins As Potential Biomarkersmentioning
confidence: 99%