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Expression of the Heterotrimeric G Protein Gi and ATP Release are Impaired in Erythrocytes of Humans with Diabetes Mellitus

  • Conference paper
Hypoxia and Exercise

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 588))

Abstract

Erythrocytes of humans have been reported to stimulate nitric oxide (NO) synthesis in the circulation as a consequence of their ability to release ATP in response to both mechanical deformation and exposure to reduced oxygen tension. It has been proposed that the ability of the erythrocyte to affect local vascular resistance permits it to participate in the regulation of blood flow such that oxygen delivery is matched with metabolic need. A signal transduction pathway that relates deformation and exposure to reduced oxygen tension to ATP release from human erythrocytes has been described. The heterotrimeric G protein, Gi, is a critical component of this pathway. Importantly, stimulation of Gi results in activation of adenylyl cyclase and ATP release from these cells. Recently, in a model of diabetes mellitus in rats, expression of Gi was reported to be decreased in the aorta. We report that expression of Gαi2 is selectively decreased in erythrocytes of humans with type 2 diabetes (DM2) and that these erythrocytes fail to release ATP in response to incubation with mastoparan 7(10 µM), an agent that activates Gi. These results provide support for the hypothesis that ATP release from erythrocytes of humans with DM2 is impaired and this defect in erythrocyte physiology could contribute to the vascular disease associated with this clinical condition.

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Authors and Affiliations

  1. Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine, St. Louis, MO, USA

    Randy Sprague, Alan Stephenson, Elizabeth Bowles, Madelyn Stumpf, Gregory Ricketts & Andrew Lonigro

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  1. Randy Sprague
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  2. Alan Stephenson
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  5. Gregory Ricketts
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  6. Andrew Lonigro
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Editors and Affiliations

  1. Altitude Research Center, University of Colorado Health Sciences Center, Mail Stop F524, PO Box 6508, Aurora, Colorado, 80045-0508

    Robert C. Roach Ph.D. (Research Director) (Research Director)

  2. UCSD Dept Medicine, 0623 9500 Gilman Avenue, La Jolla, CA, 92093-0623

    Peter D. Wagner

  3. Telluride Medical Center, 500 W. Pacific, Telluride, Colorado, 81435

    Peter H. Hackett

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Sprague, R., Stephenson, A., Bowles, E., Stumpf, M., Ricketts, G., Lonigro, A. (2006). Expression of the Heterotrimeric G Protein Gi and ATP Release are Impaired in Erythrocytes of Humans with Diabetes Mellitus. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia and Exercise. Advances in Experimental Medicine and Biology, vol 588. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-34817-9_18

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