1. Diabetes and hypertension: Pivotal involvement of purinergic signaling
- Author
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Vera Maria Morsch, Karine Paula Reichert, Milagros Fanny Vera Castro, Naiara Stefanello, Vanessa Valéria Miron, Andréia Machado Cardoso, Maria Rosa Chitolina Schetinger, Charles Elias Assmann, and Nathieli B. Bottari
- Subjects
BP, blood pressure ,HIF-1α, hypoxia-inducible factor-1α ,Adenosine ,Up4A, uridine adenosine tetraphosphate ,Cell Communication ,Review ,APCs, antigen presenting cells ,BFR, blood flow restriction ,0302 clinical medicine ,PNP, purine nucleoside phosphorylase ,Diabetic cardiomyopathy ,Purinergic P2 Receptor Antagonists ,HIAE, high intensity aerobic ,Medicine ,NOS, nitric oxide synthase ,5'-Nucleotidase ,5′-NT ,CD73, ecto-5′-nucleotidase ,Ectonucleotidases ,GLP-1, glucagon-like peptide-1 ,General Medicine ,PAP, prostatic acid phosphatase ,GLUT, glucose transporter ,NTPDase1/CD39, E-NTPDase family ,030220 oncology & carcinogenesis ,TReg, regulatory T cells ,ATP, adenosine 5′-triphosphate ,P1, purinergic receptors family 1 ,DBP, diastolic blood pressure ,RM1-950 ,ADP, adenosine 5′-diphosphate ,STZ, streptozotocin ,LIAE, low intensity aerobic exercise ,HIIT, high-intensity intermittent training ,03 medical and health sciences ,Antigens, CD ,Diabetes Mellitus ,Humans ,Exercise ,Ado, Adenosine ,PBMCs, peripheral blood mononuclear cells ,Pharmacology ,NO, nitric oxide ,Receptors, Purinergic P2 ,UTP, uridine-5′-triphosphate ,Receptors, Purinergic P1 ,T2DM, type 2 diabetes mellitus ,medicine.disease ,IL, interleukin ,CGA, chlorogenic acid ,030104 developmental biology ,Glucose ,ER, endoplasmatic reticulum ,GABA, gamma-aminobutyric acid ,Ino, inosine ,PKA, protein kinase A ,SHR, spontaneously hypertensive rat ,0301 basic medicine ,Adenosine Deaminase ,STAT3, signal transducer and activator of transcription 3 ,SIT, sprint interval training ,UDP, uridine diphosphate ,Bioinformatics ,Adenosine deaminase ,VO2máx, maximal oxygen uptake ,DM, diabetes mellitus ,E-NPP, ecto-nucleotide pyrophosphatase/phosphodiesterase ,Receptor ,ADA, adenosine deaminase ,NOD-mice, Non-obese diabetic mice ,NF-κB, nuclear factor kappa B ,TNF-α, tumor necrosis factor α ,biology ,AMP, adenosine 5′-monophosphate ,Apyrase ,T1DM, type 1 diabetes mellitus ,Purinergic receptor ,E-NTPDase, ecto-nucleoside triphosphate diphosphohydrolase ,eNOS, endothelial nitric oxide synthase ,MICT, moderate intensity continuous training ,Purinergic signalling ,IRS-1, insulin receptor substrate 1 ,VEGF, vascular endothelial growth factor ,mRNA, messenger RNA ,MSNA, muscle sympathetic nerve activity ,Hypertension ,Ap3A, diadenosine triphosphate ,Blood pressure ,Diet, Healthy ,DCs, dendritic cells ,Purinergic receptors ,Signal Transduction ,medicine.drug ,P2Y, purinergic metabotropic receptor family 2 ,TNAP, tissue-nonspecific alkaline phosphatase ,HbA1c, glycosylated hemoglobin ,P2 receptor ,CNS, central nervous system ,APs, alkaline phosphatases ,SIRT1, Sirtuin 1 ,GPCRs, G-protein-coupled receptors ,L-NAME, L-NG-nitroarginine methyl ester ,P2X, purinergic ionotropic receptor family 2 ,Diabetes mellitus ,Animals ,TXA2, thromboxane A2 ,ComputingMethodologies_COMPUTERGRAPHICS ,NLRP3, NLR family pyrin domain containing 3 ,cAMP, cyclic adenosine 5′-monophosphate ,business.industry ,SBP, systolic blood pressure ,AngII, angiotensin-II ,ATP ,AMPK, AMP-activated protein kinase ,NFAT, nuclear factor of activated T-cells ,Purinergic P1 Receptor Antagonists ,DAMP, molecular pattern associated with damage ,Purines ,TGF-β1, transforming growth factor-beta 1 ,biology.protein ,Therapeutics. Pharmacology ,business ,DAG, diacylglycerol - Abstract
Graphical abstract, Highlights • The coexistence of diabetes and hypertension represents a major risk factor for the onset of cardiovascular problems. • The purinergic signaling pathway constitutes a ubiquitous system of cell–cell communication. • Purinergic system plays a pivotal role in physiopathological conditions. • Several alterations in purine metabolism have been demonstrated in diabetes and hypertension. • Purinergic system can be an important target related to therapeutic approaches in diabetes and hypertension., Diabetes mellitus (DM) and hypertension are highly prevalent worldwide health problems and frequently associated with severe clinical complications, such as diabetic cardiomyopathy, nephropathy, retinopathy, neuropathy, stroke, and cardiac arrhythmia, among others. Despite all existing research results and reasonable speculations, knowledge about the role of purinergic system in individuals with DM and hypertension remains restricted. Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the recognition and degradation of extracellular nucleotides and adenosine. The main components of this system that will be presented in this review are: P1 and P2 receptors and the enzymatic cascade composed by CD39 (NTPDase; with ATP and ADP as a substrate), CD73 (5′-nucleotidase; with AMP as a substrate), and adenosine deaminase (ADA; with adenosine as a substrate). The purinergic system has recently emerged as a central player in several physiopathological conditions, particularly those linked to inflammatory responses such as diabetes and hypertension. Therefore, the present review focuses on changes in both purinergic P1 and P2 receptor expression as well as the activities of CD39, CD73, and ADA in diabetes and hypertension conditions. It can be postulated that the manipulation of the purinergic axis at different levels can prevent or exacerbate the insurgency and evolution of diabetes and hypertension working as a compensatory mechanism.
- Published
- 2021