FOH 8 Metabolic Syndrome.Indd

Total Page:16

File Type:pdf, Size:1020Kb

FOH 8 Metabolic Syndrome.Indd Metabolic Syndrome 3 out of 5 criteria for diagnosis Pathological levels? Fasting glucose Waist circumference Blood pressure Triglycerides HDL-Cholesterol Our Routine Laboratory Tests Intact Proinsulin Adiponectin OxLDL / MDA Adduct CRP (high sensitive) IDK® TNFa Haptoglobin Vitamin B1 Tests for your Research Adenosine Resistin ADMA Xpress Relaxin ADMA (Mouse/Rat) OPG AOPP total sRANKL Carbonylated Proteins IDK® TNFa RBP/RBP4 IDK® Zonulin US: all products: Research Use Only. Not for use in diagnostic procedures. www.immundiagnostik.com Metabolic Syndrome Adiponectin total (human) (ELISA) (K 6250) Determination of the adiponectin level as a prevention for Type-2-Diabetes Retinol-binding protein RBP/RBP4 (ELISA) (K 6110) Influence on glucose homeostasis and the development of insulin sensitivity / resistance Convenient marker for Type-2-Diabetes and for cardiovascular risk Resistin (ELISA) (on request) Link between adipositas and insulin resistance? ID Vit® Vitamin B1 (colorimetric test) (KIF001) Diabetes patients exhibit a low Vitamin B1 plasma level Also available: Other Vitamin B ID Vit® tests IDK® Zonulin (ELISA) (K 5601 ) Understanding the dynamic interaction between zonulin and diabetes. High zonulin levels are associated with Type-1-Diabetes Vasoconstriction / Vasodilatation Relaxin (ELISA) (K 9210) Endogenous antagonist of endothelin. Vasodilatator, increases microcirculation Urotensin II ( RUO) (on request) Most powerful vasoconstrictor known Oxidative Stress / Arteriosclerosis ADMA Xpress (Asymmetric Dimethylarginine) (ELISA) (K 7860 ) Endogenous NO synthase inhibitor as prognostic factor of arteriosclerosis Also available: ADMA (Mouse / Rat) ELISA (KR3001; RUO ) AOPP (Advanced Oxidation Protein Products) (Colorimetric MTP Assay) (KR7811w; RUO ) Biomarker for protein degradation by reactive oxygen species Carbonyl Protein (ELISA) (K 7870) Biomarker for oxidative stress Ultra-sensitive assay with minimal sample volume IDK® Calprotectin (MRP 8/14) (ELISA) (K 6935, K 6928 ) Granulocyte activation marker for diagnostics of inflammatory processes S100A8/A9 (Mouse/Rat) MRP 8/14 / Calprotectin) (ELISA) (KR6936; RUO) worldwide unique Granulocyte activation marker for diagnostics of inflammatory processes in research CRP (high sensitive CRP) (ELISA) (K 9710s) Risk marker of arteriosclerosis Haptoglobin (ELISA) (KSA71001) Increased oxidative stress and CVD risk in Hp 2-2 phenotype diabetes mellitus patients IDK® MPO (ELISA) (K 6631B) Indicates risk of myocardial infarction OxLDL / MDA Adduct (ELISA) (K 7810) Marker for lipid peroxidation Involved in the pathogenesis of arteriosclerosis and coronary heart disease IDK® TNFa (Tumor Nekrose Faktor a) (ELISA) (K 9610) Detection of the proinflammatory cytokine TNFa Vascular Calcification Osteoprotegerin (OPG) (ELISA) (K 1011) Part of the OPG-/RANKL/sRANKL system which plays a role in the pathogenesis of vascular diseases Serum OPG levels are associated with the presence and severity of coronary artery disease Also available: OPG Mouse/Rat (ELISA) (KR1020; RUO) total sRANKL (ELISA) (K 1016) worldwide unique Part of the OPG-/RANKL/sRANKL system which plays a role in the pathogenesis of vascular diseases Also available: sRANKL Mouse/Rat (ELISA) (K 1019; RUO) PCR Assays: MutaCHIP® ARTERO (KF390009) Cardiovascular Risk Genes MutaCHIP® TOXO (KF390011) Detoxification enzymes MutaGEL® ApoB100 (KE09023; RUO) PCR test for the detection of a mutation in codon 3500 in patients with hypercholesterolemia MutaPLATE® / REAL Prothrombin (Factor II) (KF1901696, KF291696) MutaPLATE® / REAL Factor V (KF1901796, KF291796) MutaPLATE®MTHFR 2 (TM) (KF1901496) Mutations in the MTHFR gene should be analysed conjunctively as genetic risk factors for hyperhomocysteinemia RUO: Research Use Only For more information please visit our website www.immundiagnostik.com or contact our export department [email protected] FAX-Reply to: +49 62 51 84 94 30 Immundiagnostik AG Please send me the following informative material: q 19 Brochures: Product List Product List 2019 Immunoassays HPLC • LC-MS/MS Photometry Molecular Biology q Skeletal System Immundiagnostik AG Stubenwald-Allee 8a 64625 Bensheim, Germany Phone: +49 (0) 62 51/70 19 00 Fax: +49 (0) 62 51/84 94 30 [email protected] www.immundiagnostik.com q Gastrointestinal Diseases q Cardiovascular and Renal Systems q Catalogue "IDK® Applied Bioscience & Research Products“ (Antibodies 19 q Complementary Medicine and Antigens) IDK® Applied Bioscience & Research Products q Oxidative Stress Antibodies Antigens q Molecular Biology 2019-02-05 q HPLC Applications / LC-MS/MS Applications q Manuals of these products: Name/Address: Phone: Fax: E-Mail: Date: Immundiagnostik AG Stubenwald-Allee 8a 64625 Bensheim, Germany Phone: +49 (0)6251 701900 Fax: +49 (0)6251 849430 [email protected] www.immundiagnostik.com www.immundiagnostik.com FOH 8 2019-08-19.
Recommended publications
  • Orphan G Protein-Coupled Receptors and Obesity
    European Journal of Pharmacology 500 (2004) 243–253 www.elsevier.com/locate/ejphar Review Orphan G protein-coupled receptors and obesity Yan-Ling Xua, Valerie R. Jacksonb, Olivier Civellia,b,* aDepartment of Pharmacology, University of California Irvine, 101 Theory Dr., Suite 200, Irvine, CA 92612, USA bDepartment of Developmental and Cell Biology, University of California Irvine, 101 Theory Dr, Irvine, CA 92612, USA Accepted 1 July 2004 Available online 19 August 2004 Abstract The use of orphan G protein-coupled receptors (GPCRs) as targets to identify new transmitters has led over the last decade to the discovery of 12 novel neuropeptide families. Each one of these new neuropeptides has opened its own field of research, has brought new insights in distinct pathophysiological conditions and has offered new potentials for therapeutic applications. Interestingly, several of these novel peptides have seen their roles converge on one physiological response: the regulation of food intake and energy expenditure. In this manuscript, we discuss four deorphanized GPCR systems, the ghrelin, orexins/hypocretins, melanin-concentrating hormone (MCH) and neuropeptide B/neuropeptide W (NPB/NPW) systems, and review our knowledge of their role in the regulation of energy balance and of their potential use in therapies directed at feeding disorders. D 2004 Elsevier B.V. All rights reserved. Keywords: Feeding; Ghrelin; Orexin/hypocretin; Melanin-concentrating hormone; Neuropeptide B; Neuropeptide W Contents 1. Introduction............................................................ 244 2. Searching for the natural ligands of orphan GPCRs ....................................... 244 2.1. Reverse pharmacology .................................................. 244 2.2. Orphan receptor strategy ................................................. 244 3. Orphan receptors and obesity................................................... 245 3.1. The ghrelin system .................................................... 245 3.2.
    [Show full text]
  • A Summary About Relaxin and Its Reproductive Function
    Endocrinology & Metabolism International Journal Review Article Open Access A summary about relaxin and its reproductive function Abstract Volume 4 Issue 5 - 2017 Relaxin is a pleiotropic hormone included in the insulin-like-growth factor family (IGF) Alana Aragon-Herrera,1 Sandra Feijoo- that is produced in a variety of reproductive tissues including corpus luteum, uterus, testis, Bandin,1,2 Diego Rodriguez-Penas,1 Manuel prostate and others. Relaxin facilitates parturition, participates in uterine contractility, 2,3 2,3 promotes angiogenesis, plays a role in spermatogenesis or promotes spermatozoa motility Portoles, Esther Rosello-Lleti, Miguel 2,3 1,2 and acrosome reaction, among others physiological functions. In this review, we will focus Rivera, Jose Ramon Gonzalez-Juanatey, on the principal roles of relaxin in female and male reproduction. Francisca Lago1,2 1Cellular and Molecular Cardiology Research Unit and Keywords: relaxin, reproduction, parturition, pregnancy, spermatogenesis, male Department of Cardiology of Institute of Biomedical Research reproduction, angiogenesis and University Clinical Hospital, Spain 2Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares, Spain 3La Fe University Hospital, Spain Correspondence: Alana Aragón-Herrera, Unidad de Investigación en Cardiología Celular y Molecular (7), Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Planta -2, Edificio de Consultas Externas, Hospital Clínico Universitario, Travesía Choupana s/n, 15706 Santiago de Compostela, Spain,
    [Show full text]
  • REVIEW ARTICLE Relaxin Family Peptides: Structure–Activity Relationship Studies
    British Journal of British Journal of Pharmacology (2017) 174 950–961 950 BJP Pharmacology Themed Section: Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors REVIEW ARTICLE Relaxin family peptides: structure–activity relationship studies Correspondence Mohammed Akhter Hossain, PhD, and Prof Ross A. D. Bathgate, PhD, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia. E-mail: akhter.hossain@florey.edu.au; bathgate@florey.edu.au Received 5 August 2016; Revised 25 November 2016; Accepted 28 November 2016 Nitin A Patil1,2,KJohanRosengren3, Frances Separovic2 ,JohnDWade1,2, Ross A D Bathgate1,3 and Mohammed Akhter Hossain1,2 1The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia, 2School of Chemistry, University of Melbourne, Parkville, VIC, Australia, and 3Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family peptide receptors, RXFP1–4. As these peptides play a vital role physiologically and in various diseases, they are of considerable importance for drug discovery and development. Detailed structure–activity relationship (SAR) studies towards understanding the role of important residues in each of these peptides have been reported over the years and utilized for the design of antag- onists and minimized agonist variants. This review summarizes the current knowledge of the SAR of human relaxin 2 (H2 relaxin), human relaxin 3 (H3 relaxin), human insulin-like peptide 3 (INSL3) and human insulin-like peptide 5 (INSL5). LINKED ARTICLES This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors.
    [Show full text]
  • Relaxin and the Paraventricular Nucleus of the Hypothalamus
    Relaxin and the Paraventricular Nucleus of the Hypothalamus by Megan Susan McGlashan A Thesis Presented to The University of Guelph In partial fulfillment of requirements for the degree of Master of Science in Biomedical sciences Guelph, Ontario, Canada © Megan S. McGlashan, August, 2013 ABSTRACT RELAXIN AND THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS Megan Susan McGlashan Advisor: University of Guelph, 2013 Professor A. J. S. Summerlee The hormone relaxin regulates the release of the magnocellular hormones, oxytocin and vasopressin, from the central nervous system. Studies have yet to determine whether relaxin regulates magnocellular hormone release through the circumventricular organs alone, or whether relaxin can act on the brain regions containing the magnocellular neurons as well. The paraventricular nucleus of the hypothalamus was isolated from other brain regions and maintained in vitro, in order evaluate the effects of the relaxin and relaxin-3 on the somatodendritic release of oxytocin and vasopressin. At 50 nM concentrations, relaxin induced oxytocin release, while relaxin-3 inhibited oxytocin release. Neither relaxin nor relaxin-3 had an effect on the vasopressin release, however the RXFP3 specific agonist, R3/I5, induced vasopressin release. The effect of the relaxin peptides on the electrical activity of neurons in the paraventricular nucleus was also evaluated. Relaxin depolarized magnocellular neurons while relaxin-3 hyperpolarized the neurons. Relaxin and relaxin-3 appear to have differential effects on the magnocellular neurons of the paraventricular nucleus. iii ACKNOWLEDGEMENTS When we first enter graduate school, we are very much children in the ways of research. As the saying goes, it takes a village to raise a child, so it was for my master’s degree.
    [Show full text]
  • The Role of the Relaxin Receptor RXFP1 in Brain Cancer
    The role of the relaxin receptor RXFP1 in brain cancer By Usakorn Kunanuvat A Thesis submitted to the Faculty of Graduate Studies of The University of Manitoba in partial fulfilment for the requirements of the degree of MASTER OF SCIENCE Department of Human Anatomy and Cell Science University of Manitoba Winnipeg Copyright © 2012 by Usakorn Kunanuvat ABSTRACT Relaxin (RLN2) promotes cell migration/invasion, cell growth, and neoangiogenesis through binding to the relaxin receptor RXFP1 in many types of cancers. However, there have been no studies to determine the role of this system in brain tumors, especially in Glioblastoma Multiforme (GB), the most lethal primary brain tumor in adults. GB is a systemic brain disease and aggressively invades brain tissue. In this study, we have identified RXFP1 receptor, but not RLN2, in GB cell lines and primary GB cells from patients. RLN2 treatment resulted in a significant increase in migration of GB cell line and primary GB cells. To determine molecular mechanisms that facilitate RXFP1-mediated migration in GB cells, we employed a pseudopodia assay and 2D LC-MS/MS to investigate the protein composition at cell protrusions (pseudopodia) during GB cell migration. We also observed the expression of known mediators promoting tissue invasion upon RLN2 treatment. We identified PGRMC1, a candidate protein from 2D LC-MS/MS as a novel relaxin target protein in RXFP1-expressing brain tumor cells. RLN2 treatment also caused an increase in cathepsin (cath)-B and -L and enhanced production of as the small Rho-GTPases Rac1 and Cdc42 in GB cells. Collectively, these findings indicate that RXFP1-induced cell migration is mediated by the upregulation and intracellular actions of Rac1, Cdc42 and by cath-B and cath–L who serve as matrix modulating factors to facilitate brain tumor cells migration.
    [Show full text]
  • New Insights Into Metabolic Homeostasis Keith Tan
    Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2015 Activity Based Profiling: New Insights into Metabolic Homeostasis Keith Tan Follow this and additional works at: http://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons Recommended Citation Tan, Keith, "Activity Based Profiling: New Insights into Metabolic Homeostasis" (2015). Student Theses and Dissertations. Paper 285. This Thesis is brought to you for free and open access by Digital Commons @ RU. It has been accepted for inclusion in Student Theses and Dissertations by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. ACTIVITY BASED PROFILING: NEW INSIGHTS INTO METABOLIC HOMEOSTASIS A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Keith Tan June 2015 © Copyright by Keith Tan 2015 ACTIVITY BASED PROFILING: NEW INSIGHTS INTO METABOLIC HOMEOSTASIS Keith Tan, Ph.D. The Rockefeller University 2015 There is mounting evidence that demonstrates that body weight and energy homeostasis is tightly regulated by a physiological system. This system consists of sensing and effector components that primarily reside in the central nervous system and disruption to these components can lead to obesity and metabolic disorders. Although many neural substrates have been identified in the past decades, there is reason to believe that there are numerous unidentified neural populations that play a role in energy balance. Besides regulating caloric consumption and energy expenditure, neural components that control energy homeostasis are also tightly intertwined with circadian rhythmicity but this aspect has received less attention.
    [Show full text]
  • Inflammation, Atherosclerosis, and Aspects of Insulin Action
    Reviews/Commentaries/ADA Statements PERSPECTIVES ON THE NEWS Inflammation, Atherosclerosis, and Aspects of Insulin Action ZACHARY T. BLOOMGARDEN, MD resistance is associated with increased CRP levels, insulin secretion does not it- self increase CRP (15). CRP levels in non- diabetic persons increase with worsening C-reactive protein Chait noted, CVD prevalence is greater in glycemia and particularly with postload At the American Diabetes Association persons with metabolic syndrome with- glycemia (16). Insulin resistance is asso- Postgraduate Course held in New York on out diabetes than in those with diabetes ciated with a number of inflammatory 5 February 2005, Alan Chait (Seattle, who do not have the metabolic syndrome markers in addition to CRP, such as se- WA) discussed C-reactive protein (CRP). (13). Similarly, a study of persons from cretory phospholipase A2, e-selectin, and Although it may not be as predictive of Botnia in Finland showed, that for all lev- ICAM-1 (17). In the context of insulin re- cardiovascular disease (CVD) as choles- els of glycemia, the presence of metabolic sistance, obese persons have improve- terol, hypertension, and cigarette use (1), syndrome is associated with an increase in ment in insulin sensitivity and in CRP CRP appears to be the strongest “novel” CVD prevalence (14). The metabolic syn- with weight loss, while obese persons risk factor thus far identified, showing drome, then, is both associated with in- with normal insulin sensitivity, whose greater predictive power than homocys- flammation and appears to be a CRP level is lower, do not show further teine, interleukin (IL)-6 (2), and other in- particularly important marker of CVD decrease following weight loss, suggest- flammatory markers, such as serum risk.
    [Show full text]
  • Distribution, Physiology and Pharmacology of Relaxin-3/RXFP3 Systems in Brain
    British Journal of British Journal of Pharmacology (2017) 174 1034–1048 1034 BJP Pharmacology Themed Section: Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors REVIEW ARTICLE Distribution, physiology and pharmacology of relaxin-3/RXFP3 systems in brain Correspondence Andrew L. Gundlach, The Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, Parkville, Victoria 3052, Australia. E-mail: andrew.gundlach@florey.edu.au Received 25 July 2016; Revised 12 October 2016; Accepted 17 October 2016 Sherie Ma1,2,CraigMSmith1,2,3,AnnaBlasiak4 and Andrew L Gundlach1,2,5 1The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia, 2Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria Australia, 3School of Medicine, Deakin University, Geelong, Victoria, Australia, 4Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University, Krakow, Poland, and 5Department of Anatomy and Neuroscience, The University of Melbourne, Victoria, Australia Relaxin-3 is a member of a superfamily of structurally-related peptides that includes relaxin and insulin-like peptide hormones. Soon after the discovery of the relaxin-3 gene, relaxin-3 was identified as an abundant neuropeptide in brain with a distinctive topographical distribution within a small number of GABAergic neuron populations that is well conserved across species. Relaxin- 3 is thought to exert its biological actions through a single class-A GPCR – relaxin-family peptide receptor 3 (RXFP3). Class-A comprises GPCRs for relaxin-3 and insulin-like peptide-5 and other peptides such as orexin and the monoamine transmitters. The RXFP3 receptor is selectively activated by relaxin-3, whereas insulin-like peptide-5 is the cognate ligand for the related RXFP4 receptor.
    [Show full text]
  • Pulmonary Function Changes in Older Adults with and Without Metabolic
    www.nature.com/scientificreports OPEN Pulmonary function changes in older adults with and without metabolic syndrome Maysa Alves Rodrigues Brandao‑Rangel1,2*, Renilson Moraes‑Ferreira1,2, Manoel Carneiro Oliveira‑Junior2, Alana Santos‑Dias2, André Luis Lacerda Bachi2,3, Giovana Gabriela‑Pereira2, Simone de Oliveira Freitas2, Amanda Cristina Araújo‑Rosa1,2, Luis Vicente Franco Oliveira4, Claudio Ricardo Frison2, Wagner Luiz do Prado5, Raghavan Pillai Raju6, P Babu Balagopal7,8,9 & Rodolfo P Vieira1,2,10 The low‑grade infammation associated with metabolic syndrome (MS) triggers functional and structural alterations in several organs. Whereas lung function impairment is well reported for older adult population, the efect of MS on functional and immunological responses in the lungs remains unclear. In this cross‑sectional study we determined whether MS alters pulmonary function, and immunological responses in older adults with MS. The study sample consisted of older adults with MS (68 ± 3 years old; n = 77) and without MS (67 ± 3 years old; n = 77). Impulse oscillometry was used to evaluate airway and tissue resistance, and reactance. Biomarkers of infammation and fbrosis were assessed in the blood and in breath condensate. The total resistance of the respiratory system (R5Hz; p < 0.009), and the resistance of the proximal (R20Hz; p < 0.001) and distal (R5Hz–R20Hz; p < 0.004) airways were higher in MS individuals compared to those without MS. Pro‑infammatory (leptin, IL‑1beta, IL‑8, p < 0.001; TNF‑alpha, p < 0.04) and anti‑infammatory cytokines (adiponectin, IL‑1ra, IL‑10, p < 0.001), anti‑fbrotic (relaxin 1, relaxin 3, Klotho, p < 0.001) and pro‑fbrotic (VEGF, p < 0.001) factors were increased in sera and in breath condensate individuals with MS.
    [Show full text]
  • Interplay of Adipokines in the Pathogenesis of Essential Hypertension: a Comparative Cross-Sectional in Ghana ⇑ Osei Asibey A,B, , Francis Agyemang Yeboah A, W.K.B.A
    Alexandria Journal of Medicine 54 (2018) 469–474 Contents lists available at ScienceDirect Alexandria Journal of Medicine journal homepage: http://www.elsevier.com/locate/ajme Original Article Interplay of adipokines in the pathogenesis of essential hypertension: A comparative cross-sectional in Ghana ⇑ Osei Asibey a,b, , Francis Agyemang Yeboah a, W.K.B.A. Owiredu a, Emmanuel Acheampong a,c, Enoch Odame Anto a,c, Isaac K. Owusu d a Department of Molecular Medicine, School of Medical Science, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana b Department of Clinical Biochemistry, Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana c School of Medical and Health Sciences, Edith Cowan University, Western Australia, Australia d Department of Medicine, Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana article info abstract Article history: Background: The renin-angiotensin-system (RAS), endothelial dysfunction and sympathetic nervous sys- Received 7 May 2018 tem are mechanistic risk factors of hypertension. The study sought to elucidate the interplay of adipoki- Revised 4 July 2018 nes in the pathogenesis of essential hypertension. Accepted 17 July 2018 Methodology: This comparative cross-sectional study recruited 200 confirmed hypertensive patients Available online 31 July 2018 from the KATH and 50 age-matched normotensives. Participants’ blood pressures, anthropometric and socio-demographic information were voluntarily obtained. Serum levels of adiponectin, leptin and resis- Keywords: tin of the participants were quantified using the ELISA. Renal function, lipid profile and glycemic status of Adipokines all subjects were also analyzed. Hypertension Leptin Results: Hypertensive patients showed a significantly higher anthropometric indices of adiposity Adiponectin compared to normotensives, CI (p < 0.0001), BAI (p < 0.0001) and AVI (p = 0.002).
    [Show full text]
  • RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice Via a Gαi2-Protein/Pi3kß/Γ/Nitric Oxide-Coupled Pathway
    fphys-09-01234 September 1, 2018 Time: 10:24 # 1 ORIGINAL RESEARCH published: 04 September 2018 doi: 10.3389/fphys.2018.01234 RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a Gai2-Protein/PI3Kß/g/Nitric Oxide-Coupled Pathway Xiaoming Lian1, Sandra Beer-Hammer2, Gabriele M. König3, Evi Kostenis3, Bernd Nürnberg2 and Maik Gollasch1,4* 1 Experimental and Clinical Research Center (ECRC), Charité – University Medicine Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, 2 Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, and Interfaculty Center of Pharmacogenomics and Drug Research (ICePhA), Tübingen, Germany, 3 Institute for Pharmaceutical Biology, University of Bonn, Bonn, Germany, 4 Medical Clinic for Nephrology and Internal Intensive Care, Charité Campus Virchow Klinikum, Berlin, Germany Edited by: Camille M. Balarini, Background: Relaxins are small peptide hormones, which are novel candidate Federal University of Paraíba, Brazil molecules that play important roles in cardiometablic syndrome. Relaxins are Reviewed by: structurally related to the insulin hormone superfamily, which provide vasodilatory Ulf Simonsen, effects by activation of G-protein-coupled relaxin receptors (RXFPs) and stimulation Aarhus University, Denmark Anna M. D. Watson, of endogenous nitric oxide (NO) generation. Recently, relaxin could be demonstrated Monash University, Australia to activate Gi proteins and phosphoinositide 3-kinase (PI3K) pathways in cultured *Correspondence: endothelial cells in vitro. However, the contribution of the Gi-PI3K pathway and their Maik Gollasch [email protected] individual components in relaxin-dependent relaxation of intact arteries remains elusive.
    [Show full text]
  • An Adiponectin-S1P Autocrine Axis Protects Skeletal Muscle Cells From
    Botta et al. Lipids in Health and Disease (2020) 19:156 https://doi.org/10.1186/s12944-020-01332-5 RESEARCH Open Access An adiponectin-S1P autocrine axis protects skeletal muscle cells from palmitate- induced cell death Amy Botta, Kazaros Elizbaryan, Parastoo Tashakorinia, Nhat Hung Lam and Gary Sweeney* Abstract Background: The prevalence of type 2 diabetes, obesity and their various comorbidities have continued to rise. In skeletal muscle lipotoxicity is well known to be a contributor to the development of insulin resistance. Here it was examined if the small molecule adiponectin receptor agonist AdipoRon mimicked the effect of adiponectin to attenuate palmitate induced reactive oxygen species (ROS) production and cell death in L6 skeletal muscle cells. Methods: L6 cells were treated ±0.1 mM PA, and ± AdipoRon, then assays analyzing reactive oxygen species (ROS) production and cell death, and intracellular and extracellular levels of sphingosine-1 phosphate (S1P) were conducted. To determine the mechanistic role of S1P gain (using exogenous S1P or using THI) or loss of function (using the SKI-II) were conducted. Results: Using both CellROX and DCFDA assays it was found that AdipoRon reduced palmitate-induced ROS production. Image-IT DEAD, MTT and LDH assays all indicated that AdipoRon reduced palmitate-induced cell death. Palmitate significantly increased intracellular accumulation of S1P, whereas in the presence of AdipoRon there was increased release of S1P from cells to extracellular medium. It was also observed that direct addition of extracellular S1P prevented palmitate-induced ROS production and cell death, indicating that S1P is acting in an autocrine manner. Pharmacological approaches to enhance or decrease S1P levels indicated that accumulation of intracellular S1P correlated with enhanced cell death.
    [Show full text]