title: Adenosine signalling in diabetes mellitus--pathophysiology and therapeutic considerations.
abstract: Adenosine is a key extracellular signalling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors, A1, A2A, A2B and A1 adenosine receptors. Accumulating evidence highlights a critical role for the adenosine system in the regulation of glucose homeostasis and the pathophysiology of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Although adenosine signalling is known to affect insulin secretion, new data indicate that adenosine signalling also contributes to the regulation of β-cell homeostasis and activity by controlling the proliferation and regeneration of these cells as well as the survival of β cells in inflammatory microenvironments. Furthermore, adenosine is emerging as a major regulator of insulin responsiveness by controlling insulin signalling in adipose tissue, muscle and liver; adenosine also indirectly mediates effects on inflammatory and/or immune cells in these tissues. This Review critically discusses the role of the adenosine-adenosine receptor system in regulating both the onset and progression of T1DM and T2DM, and the potential of pharmacological manipulation of the adenosinergic system as an approach to manage T1DM, T2DM and their associated complications.
authors: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors: Luca
authors: L
authors: Antonioli
authors: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors: Corrado
authors: C
authors: Blandizzi
authors: Department of Surgery and Center for Immunity and Inflammation, Rutgers-New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, NJ 07103, USA.
authors: Balázs
authors: B
authors: Csóka
authors: Section on Oxidative Stress Tissue Injury, Laboratories of Physiological Studies, NIH/NIAAA, 5625 Fishers Lane, Bethesda, MD 20892, USA.
authors: Pál
authors: P
authors: Pacher
authors: Department of Surgery and Center for Immunity and Inflammation, Rutgers-New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, NJ 07103, USA.
authors: György
authors: G
authors: Haskó
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007333:Insulin Resistance; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018047:Receptors, Purinergic P1; D000241:Adenosine