Reduced expression of G(i) in erythrocytes of humans with type 2 diabetes is associated with impairment of both cAMP generation and ATP release.
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 platelets of humans with type 2 diabetes. Here, we report that G(i2) expression is selectively decreased in erythrocytes of humans with type 2 diabetes and that this defect is associated with reductions in cAMP accumulation and ATP release in response to incubation of erythrocytes with mastoparan 7 (10 micromol/l), an activator of G(i). Importantly, this defect in ATP release correlates inversely with the adequacy of glycemic control as determined by levels of HbA(1c) (A1C). These results demonstrate that in erythrocytes of humans with type 2 diabetes, both G(i) expression and ATP release in response to mastoparan 7 are impaired, which is consistent with the hypothesis that this defect in erythrocyte physiology could contribute to the vascular disease associated with this clinical condition.
Sprague
Randy S
RS
Saint Louis University, School of Medicine, Department of Pharmacological and Physiological Science, 1402 South Grand Blvd., St. Louis, MO 63104, USA. spraguer@slu.edu
Stephenson
Alan H
AH
Bowles
Elizabeth A
EA
Stumpf
Madelyn S
MS
Lonigro
Andrew J
AJ
D000255:Adenosine Triphosphate / Q000097:blood*; D000242:Cyclic AMP / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000097:blood*; D006442:Glycated Hemoglobin; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000494:pharmacology; D012016:Reference Values
D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D006442:Glycated Hemoglobin; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C084070:Mas7 protein, synthetic