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Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent actions of insulin to stimulate production of NO from endothelial cells.

Published on Mar 1, 2007in American Journal of Physiology-endocrinology and Metabolism 4.13
· DOI :10.1152/ajpendo.00570.2006
Micaela Iantorno18
Estimated H-index: 18
,
Hui Chen33
Estimated H-index: 33
+ 4 AuthorsMichael J. Quon74
Estimated H-index: 74
Cite
Abstract
Ghrelin is an orexigenic peptide hormone secreted by the stomach. In patients with metabolic syndrome and low ghrelin levels, intra-arterial ghrelin administration acutely improves their endothelial dysfunction. Therefore, we hypothesized that ghrelin activates endothelial nitric oxide synthase (eNOS) in vascular endothelium, resulting in increased production of nitric oxide (NO) using signaling pathways shared in common with the insulin receptor. Similar to insulin, ghrelin acutely stimulated increased production of NO in bovine aortic endothelial cells (BAEC) in primary culture (assessed using NO-specific fluorescent dye 4,5-diaminofluorescein) in a time- and dose-dependent manner. Production of NO in response to ghrelin (100 nM, 10 min) in human aortic endothelial cells was blocked by pretreatment of cells with NG-nitro-l-arginine methyl ester (nitric oxide synthase inhibitor), wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor], or (d-Lys3)-GHRP-6 (selective antagonist of ghrelin receptor GHSR-1...
  • References (79)
  • Citations (84)
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References79
Newest
Published on Jun 1, 2008in Endocrine Reviews 15.17
Stephanie T. Page31
Estimated H-index: 31
(UW: University of Washington),
John K. Amory38
Estimated H-index: 38
(UW: University of Washington),
William J. Bremner68
Estimated H-index: 68
(UW: University of Washington)
Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicul...
Published on Jun 1, 2007in Atherosclerosis 4.25
Fabio Rossi5
Estimated H-index: 5
(Policlinico Umberto I),
Cora Bertone8
Estimated H-index: 8
(Policlinico Umberto I)
+ 1 AuthorsVittorio Santiemma5
Estimated H-index: 5
(Policlinico Umberto I)
Abstract Ghrelin, the endogenous ligand for the GH secretagogue receptor, is produced by the oxyntic cells of the stomach and is involved in the regulation of energy balance. However, an increasing number of direct ghrelin cardiovascular effects, and, among them, high ghrelin binding in atherosclerotic coronary arteries, are being reported. We investigated whether ghrelin affects migration of human aorta endothelial cells (HAEC). HAEC bound ghrelin in specific, saturable manner. Ghrelin, as such...
Published on Dec 1, 2006in Molecular Endocrinology 3.63
Roberta Avallone2
Estimated H-index: 2
(UdeM: Université de Montréal),
Annie Demers10
Estimated H-index: 10
(UdeM: Université de Montréal)
+ 7 AuthorsAndré Tremblay16
Estimated H-index: 16
(UdeM: Université de Montréal)
Macrophages play a central role in the pathogenesis of atherosclerosis by accumulating cholesterol through increased uptake of oxidized low-density lipoproteins by scavenger receptor CD36, leading to foam cell formation. Here we demonstrate the ability of hexarelin, a GH-releasing peptide, to enhance the expression of ATP-binding cassette A1 and G1 transporters and cholesterol efflux in macrophages. These effects were associated with a transcriptional activation of nuclear receptor peroxisome pr...
Published on Dec 1, 2006in Diabetes 7.20
Maria Assunta Potenza16
Estimated H-index: 16
,
Flora L. Marasciulo6
Estimated H-index: 6
+ 2 AuthorsMonica Montagnani27
Estimated H-index: 27
Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, an...
Published on Sep 1, 2006in American Journal of Hypertension 2.53
Ursula Mager9
Estimated H-index: 9
,
Marjukka Kolehmainen32
Estimated H-index: 32
+ 8 AuthorsLeena Pulkkinen22
Estimated H-index: 22
Background Ghrelin is a gut–brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. Methods The F...
Published on Jul 3, 2006in Journal of Clinical Investigation 12.28
Claudia Theander-Carrillo4
Estimated H-index: 4
,
Petra Wiedmer13
Estimated H-index: 13
+ 9 AuthorsIldiko Szanto16
Estimated H-index: 16
Manyhomeostaticprocesses,�includingappetiteandfoodintake,�arecontrolledbyneuroendocrinecircuits� involvingtheCNS.�TheCNSalsodirectlyregulatesadipocytemetabolism,�aswehaveshownherebyexamin- ingcentralactionoftheorexigenichormoneghrelin.�Chroniccentralghrelininfusionresultedinincreases� intheglucoseutilizationrateofwhiteandbrownadiposetissuewithoutaffectingskeletalmuscle.�Inwhite� adipocytes,�mRNAexpressionofvariousfatstorage-promotingenzymessuchaslipoproteinlipase,�acetyl- CoAcarboxylasea,�fattya...
Published on Jul 3, 2006in Journal of Clinical Investigation 12.28
Leona Plum18
Estimated H-index: 18
,
Bengt F. Belgardt15
Estimated H-index: 15
,
Jens C. Brüning66
Estimated H-index: 66
(University of Cologne)
Insulinhaspleiotropicbiologicaleffectsinvirtuallyalltissues.�However,�therelevanceofinsulinsignalinginperiph- eraltissueshasbeenstudiedfarmoreextensivelythanitsroleinthebrain.�Anevolvingbodyofevidenceindicates� thatinthebrain,�insulinisinvolvedinmultipleregulatorymechanismsincludingneuronalsurvival,�learning,�and� memory,�aswellasinregulationofenergyhomeostasisandreproductiveendocrinology.�Herewereviewinsulin's� roleasacentralhomeostaticsignalwithregardtoenergyandglucosehomeostasisanddiscussthem...
Published on Jul 1, 2006in Journal of Internal Medicine 6.05
Seppo M. Pöykkö10
Estimated H-index: 10
,
Eija Kellokoski6
Estimated H-index: 6
+ 4 AuthorsSohvi Hörkkö5
Estimated H-index: 5
PoykkoSM, Kellokoski E, Ukkola O, Kauma H, Paivansalo M, Kesaniemi YA, HorkkoS (Biocenter Oulu; and University of Oulu; Oulu, Finland) Plasma ghrelin concentrations are positively associated with carotid artery athero- sclerosis in males. J Intern Med 2006; 260: 43-52. Background. Ghrelin, a peptide hormone from stomach, stimulates food intake and decreases fat utilization. Ghrelin binds to growth hormone secretagogue receptor (GHSR). GHSR density has been shown to be upregulated in atherosclero...
Published on Jul 1, 2006in American Journal of Hypertension 2.53
Agnieszka Kawczynska-Drozdz1
Estimated H-index: 1
(Jagiellonian University),
Rafał Olszanecki22
Estimated H-index: 22
(Jagiellonian University)
+ 4 AuthorsTomasz J. Guzik45
Estimated H-index: 45
(Jagiellonian University)
Background Ghrelin is a novel peptide involved in the control of appetite, but its role in vascular pathologies remains to be elucidated. Ghrelin was shown to decrease blood pressure (BP) and improve endothelial function. Its plasma levels are correlated with BP in humans. Mechanisms of these effects are unknown. Because oxidative stress and increased superoxide production by NAD(P)H oxidases (Nox) are critical in the pathogenesis of hypertension, we aimed to study the effects of ghrelin on vasc...
Published on Jun 1, 2006in Diabetic Medicine 3.11
Ursula Mager9
Estimated H-index: 9
,
Virpi Lindi25
Estimated H-index: 25
+ 9 AuthorsMarkku Laakso29
Estimated H-index: 29
Aims Ghrelin is a gut–brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). Methods DPS was a longitudinal intervention study carr...
Cited By84
Newest
Published on Nov 12, 2018in Artificial Cells Nanomedicine and Biotechnology 4.46
Lingyan Cao4
Estimated H-index: 4
(SJTU: Shanghai Jiao Tong University),
Xiangjun Kong2
Estimated H-index: 2
(ECUST: East China University of Science and Technology)
+ 4 AuthorsJiangXinquan33
Estimated H-index: 33
(SJTU: Shanghai Jiao Tong University)
AbstractA promising strategy to accelerate bone generation is to deliver a combination of certain growth factors to the integration site via a controlled spatial and temporal delivery mode. Here, a...
Published on Jun 1, 2018in Pflügers Archiv: European Journal of Physiology 3.38
Mohammed Saeed Zayed Al-Ayed1
Estimated H-index: 1
(Najran University)
This study aimed at investigating the potential ghrelin relaxing effect on guinea pig isolated tracheal smooth muscle (TSM). Using an in vitro experimental approach, the physiological role of the airway epithelium on smooth muscle relaxation has been investigated by analyzing the dose-response curves for carbachol- or histamine-induced contractions on epithelium intact versus denuded tracheal tissue. The relaxant effect of ghrelin (5–200 μmol/L) then investigated on carbachol-contracted, non-sen...
Published on May 1, 2018in Biomedicine & Pharmacotherapy 3.74
Refaat A. Eid11
Estimated H-index: 11
(King Khalid University),
Mohamed Samir Ahmed Zaki3
Estimated H-index: 3
(King Khalid University)
+ 7 AuthorsMahmoud A. Alkhateeb10
Estimated H-index: 10
(King Saud bin Abdulaziz University for Health Sciences)
Abstract This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghre...
Published on Mar 1, 2018in Life Sciences 3.45
Gabriel Camargo-Silva2
Estimated H-index: 2
,
Larissa Córdova Turones2
Estimated H-index: 2
+ 14 AuthorsRoger Luis Henschel Pobbe7
Estimated H-index: 7
Abstract Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. Aims In the present study, we assessed the role of ghrelin – GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Main meth...
Claudia Penna31
Estimated H-index: 31
(UNITO: University of Turin),
Francesca Tullio16
Estimated H-index: 16
(UNITO: University of Turin)
+ 10 AuthorsMaria Felice Brizzi31
Estimated H-index: 31
(UNITO: University of Turin)
Patients with ischaemic heart disease or chronic heart failure show altered levels of obestatin, suggesting a role for this peptide in human heart function. We have previously demonstrated that GH secretagogues and the ghrelin gene-derived peptides, including obestatin, exert cardiovascular effects by modulating cardiac inotropism and vascular tone, and reducing cell death and contractile dysfunction in hearts subjected to ischaemia/reperfusion (I/R), through the Akt/nitric oxide (NO) pathway. H...
Published on Jul 1, 2017in Archives of Medical Research 1.90
Michela Zanetti29
Estimated H-index: 29
(UniTS: University of Trieste),
Gianluca Gortan Cappellari9
Estimated H-index: 9
(UniTS: University of Trieste)
+ 4 AuthorsRocco Barazzoni28
Estimated H-index: 28
(UniTS: University of Trieste)
Objective Ghrelin, a gastric hormone with pleiotropic effects modulates vascular function and may influence atherosclerosis. Plasma ghrelin is reduced in the metabolic syndrome (MS), which is also characterized by early atherosclerosis. Ghrelin circulates in acylated (AG) and desacylated (DAG) forms. Their relative impact and that of gender on subclinical atherosclerosis in MS is unknown. Aim of the Study To investigate potential associations of total, AG and DAG with carotid atherosclerosis and...
Published on Feb 1, 2017in European Journal of Endocrinology 5.11
Cecilia J Zhang1
Estimated H-index: 1
(Duke University),
Martin Bidlingmaier47
Estimated H-index: 47
+ 4 AuthorsJenny Tong32
Estimated H-index: 32
(UC: University of Cincinnati)
Objective: To compare the effects of acyl ghrelin (AG) and desacyl ghrelin (DAG) on blood pressure (BP), heart rate (HR) and other autonomic parameters in healthy humans and to elucidate the hormonal mechanisms through which AG could exert its cardiovascular effects. Design: Seventeen healthy participants underwent frequent monitoring of systolic (sBP) and diastolic blood pressure (dBP), HR, respiratory rate (RR) and body surface temperature (Temp) during continuous infusion of AG, DAG, combined...
Published on Jun 1, 2016in Journal of Cardiovascular Pharmacology 2.37
Agostino Virdis53
Estimated H-index: 53
,
Stefano Taddei59
Estimated H-index: 59
A large body of homogeneous reports documented that endothelial dysfunction, which characterizes human essential hypertension is largely dependent on an impaired endothelial nitric oxide availability and an increased production of endothelium-derived contracting factors. These factors include endothelin, prostanoids, and reactive oxygen species (ROS). In particular, it was evidenced that acute intraarterial administration of indomethacin, a nonselective cyclooxygenase (COX)-inhibitor, and ascorb...
Published on Feb 1, 2016in Current Hypertension Reports 3.61
Yuanjie Mao7
Estimated H-index: 7
(Cleveland Clinic),
Takeshi Tokudome22
Estimated H-index: 22
,
Ichiro Kishimoto36
Estimated H-index: 36
Ghrelin is a growth hormone-releasing polypeptide that was first isolated from the rat stomach in 1999. High expression of growth hormone secretagogue receptor, the ghrelin receptor, in the heart, kidney, and blood vessels provides evidence of ghrelin activity in blood pressure regulation. Circulating ghrelin concentrations are reported to be inversely correlated with blood pressure, and the acute and chronic effects of ghrelin in decreasing blood pressure have been reported in animals with norm...