The Purinergic Landscape of Type 2 Diabetes Mellitus |
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Authors: | Rocio Edith Garcia-Jacobo,Leticia Scussel Bergamin,Valentina Vultaggio-Poma,Maria Luiza Thorstenberg,Mario Tarantini,Mariana Haydee Garcí a-Herná ndez,Francesco Di Virgilio |
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Affiliation: | 1.Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy; (R.E.G.-J.); (L.S.B.); (V.V.-P.); (M.L.T.); (M.T.);2.Unidad de Investigación Biomédica, Delegación Zacatecas, Instituto Mexicano del Seguro Social, IMSS, Zacatecas 98000, Mexico; |
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Abstract: | Adenosine triphosphate (ATP) is the key energy intermediate of cellular metabolic processes and a ubiquitous extracellular messenger. As an extracellular messenger, ATP acts at plasma membrane P2 receptors (P2Rs). The levels of extracellular ATP (eATP) are set by both passive and active release mechanisms and degradation processes. Under physiological conditions, eATP concentration is in the low nanomolar range but can rise to tens or even hundreds of micromoles/L at inflammatory sites. A dysregulated eATP homeostasis is a pathogenic factor in several chronic inflammatory diseases, including type 2 diabetes mellitus (T2DM). T2DM is characterized by peripheral insulin resistance and impairment of insulin production from pancreatic β-cells in a landscape of systemic inflammation. Although various hypoglycemic drugs are currently available, an effective treatment for T2DM and its complications is not available. However, counteracting systemic inflammation is anticipated to be beneficial. The postulated eATP increase in T2DM is understood to be a driver of inflammation via P2X7 receptor (P2X7R) activation and the release of inflammatory cytokines. Furthermore, P2X7R stimulation is thought to trigger apoptosis of pancreatic β-cells, thus further aggravating hyperglycemia. Targeting eATP and the P2X7R might be an appealing novel approach to T2DM therapy. |
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Keywords: | extracellular ATP P2X7 receptor type 2 diabetes mellitus inflammation |
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