scholarly journals Metabolic and Cardiovascular Effects of Ghrelin

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Manfredi Tesauro ◽  
Francesca Schinzari ◽  
Miriam Caramanti ◽  
Renato Lauro ◽  
Carmine Cardillo
Keyword(s):  
Nitric Oxide ◽  
Growth Hormone ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Amino Acid Peptide

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized as a preprohormone and then proteolytically processed to yield a 28-amino acid peptide. This peptide was originally reported to induce growth hormone release; large evidence, however, has indicated many other physiological activities of ghrelin, including regulation of food intake and energy balance, as well as of lipid and glucose metabolism. Ghrelin receptors have been detected in the hypothalamus and the pituitary, but also in the cardiovascular system, where ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely improves endothelial dysfunction by increasing nitric oxide bioavailability and normalizes the altered balance between endothelin-1 and nitric oxide within the vasculature of patients with metabolic syndrome. Other cardiovascular effects of ghrelin include improvement of left ventricular contractility and cardiac output, as well as reduction of arterial pressure and systemic vascular resistance. In addition, antinflammatory and antiapoptotic actions of ghrelin have been reported both in vivo and in vitro. This review summarizes the most recent findings on the metabolic and cardiovascular effects of ghrelin through GH-dependent and -independent mechanisms and the possible role of ghrelin as a therapeutic molecule for treating cardiovascular diseases.

scholarly journals Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion: Potential Role of Ghrelin

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4800-4812 ◽  
Author(s):  
José Córdoba-Chacón ◽  
Manuel D. Gahete ◽  
Ana I. Pozo-Salas ◽  
Antonio J. Martínez-Fuentes ◽  
Luis de Lecea ◽  
...  
Keyword(s):  
Metabolic Phenotype ◽  
Somatostatin Analogue ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ancestral Gene ◽  
Ghrelin Receptor ◽  
Physiological Relevance

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort−/−) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort−/− mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort−/− in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort−/− mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort−/− mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.

scholarly journals Development of a Spinal Cord Injury Model Permissive to Study the Cardiovascular Effects of Rehabilitation Approaches Designed to Induce Neuroplasticity

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1006
Author(s):  
Liisa Wainman ◽  
Erin L. Erskine ◽  
Mehdi Ahmadian ◽  
Thomas Matthew Hanna ◽  
Christopher R. West
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Clinical Model ◽  
Cord Injury ◽  
Hemodynamic Function ◽  
Cervical Injuries

As primary medical care for spinal cord injury (SCI) has improved over the last decades there are more individuals living with neurologically incomplete (vs. complete) cervical injuries. For these individuals, a number of promising therapies are being actively researched in pre-clinical settings that seek to strengthen the remaining spinal pathways with a view to improve motor function. To date, few, if any, of these interventions have been tested for their effectiveness to improve autonomic and cardiovascular (CV) function. As a first step to testing such therapies, we aimed to develop a model that has sufficient sparing of descending sympathetic pathways for these interventions to target yet induces robust CV impairment. Twenty-six Wistar rats were assigned to SCI (n = 13) or naïve (n = 13) groups. Animals were injured at the T3 spinal segment with 300 kdyn of force. Fourteen days post-SCI, left ventricular (LV) and arterial catheterization was performed to assess in vivo cardiac and hemodynamic function. Spinal cord lesion characteristics along with sparing in catecholaminergic and serotonergic projections were determined via immunohistochemistry. SCI produced a decrease in mean arterial pressure of 17 ± 3 mmHg (p < 0.001) and left ventricular contractility (end-systolic elastance) of 0.7 ± 0.1 mmHg/µL (p < 0.001). Our novel SCI model produced significant decreases in cardiac and hemodynamic function while preserving 33 ± 9% of white matter at the injury epicenter, which we believe makes it a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity.

scholarly journals Ghrelin and Des-Acyl Ghrelin Promote Differentiation and Fusion of C2C12 Skeletal Muscle Cells

2007 ◽  
Vol 18 (3) ◽  
pp. 986-994 ◽  
Author(s):  
Nicoletta Filigheddu ◽  
Viola F. Gnocchi ◽  
Marco Coscia ◽  
Miriam Cappelli ◽  
Paolo E. Porporato ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Ectopic Expression ◽  
Cell Types ◽  
C2c12 Cells ◽  
Growth Hormone Secretagogue Receptor ◽  
Endocrine Activity ◽  
Growth Hormone Secretagogue ◽  
Inhibition Of Proliferation ◽  
Acyl Ghrelin

Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. Inhere we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms.

scholarly journals Metabolic and cardiovascular effects of ghrelin

2012 ◽  
Vol 9 (1) ◽  
pp. 3-8 ◽  
Author(s):  
E V Kirienkova ◽  
L S Litvinova ◽  
V I Seledtsov ◽  
P A Zatolokin ◽  
N N Aksenova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Hormone ◽  
Growth Hormone Receptor ◽  
Cardiovascular Effects ◽  
Vascular Wall ◽  
Therapeutic Approaches ◽  
Extreme Caution ◽  
Amino Acid Peptide ◽  
Metabolic Functions

Ghrelin is an endogenous ligand for growth hormone receptor, which is synthesized as a prohormone, and then proteolytically converted into 28-amino acid peptide. This peptide stimulates the secretion of growth hormone, regulates food intake, effect on carbohydrate and lipid metabolism. Ghrelin enhances the bioavailability of nitric oxide and maintains the balance between endothelin-1 and nitric oxide in the vascular wall. It increases cardiac output, and reduces blood pressure and systemic vascular resistance. Antiinflammatory effect of ghrelin is also appreciated. Since ghrelin is a circulating peptide that stimulates appetite and regulate energy balance, and its role in the development of obesity and type 2 diabetes it is the subject of intense research. A variety of metabolic functions of ghrelin requires extreme caution in the use of therapeutic approaches aimed at the stimulation or blockade of its action.

scholarly journals Molecular characterization of the bovine <i>GHRL</i> gene (Short Communication)

2009 ◽  
Vol 52 (1) ◽  
pp. 79-84 ◽  
Author(s):  
F. G. Colinet ◽  
D. Portetelle ◽  
R. Renaville
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Short Communication ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Endogenous Ligand ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Amino Acid Peptide

Abstract. Bovine ghrelin, a 27 amino acid peptide, has been identified in oxyntic glands of the abomasum. It is an endogenous ligand for growth hormone secretagogue receptor and stimulates food intake and growth hormone secretion. The bovine GHRL gene was completely sequenced and consists of five exons and four introns. Like mouse and human GHRL genes, we found that the bovine GHRL gene also contains a first non-coding exon of 21 bp. The bovine GHRL gene codes for 116 amino acid peptide named preproghrelin which contains the ghrelin peptide and another peptide similar to obestatin. Sequence analysis revealed eight polymorphisms, which are located in the non-coding sequence of the gene.

scholarly journals Ghrelin in rat pancreatic islets decreases islet blood flow

2019 ◽  
Vol 317 (1) ◽  
pp. E139-E146 ◽  
Author(s):  
Carl Johan Drott ◽  
Petra Franzén ◽  
Per-Ola Carlsson
Keyword(s):  
Blood Flow ◽  
Insulin Response ◽  
Physiological Mechanism ◽  
Growth Hormone Secretagogue Receptor ◽  
Flow Measurements ◽  
Growth Hormone Secretagogue ◽  
Islet Blood Flow ◽  
Fasted Rats

The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the ε-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1α), exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1α receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1α was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats, only, also improved the peak insulin response to glucose in vivo, thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.

Ghrelin Based Therapy of Metabolic Diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Yuan Liang ◽  
Wenzhen Yin ◽  
Yue Yin ◽  
Weizhen Zhang
Keyword(s):  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Peptide Hormone ◽  
Endogenous Ligand ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Amino Acid Peptide

Background: Ghrelin, a unique 28 amino acid peptide hormone secreted by the gastric X/A like cells, is an endogenous ligand of the growth hormone secretagogue receptor (GHSR). Ghrelin-GHSR signaling has been found to exert various physiological functions including stimulation of appetite, regulation of body weight, lipid and glucose metabolism, and increase of gut motility and secretion. This system is thus critical for energy homeostasis. Objective: The objective of this review is to highlight the strategies of ghrelin-GHSR based intervention for therapy of obesity and its related metabolic diseases. Results: Therapeutic strategies of metabolic disorders targeting the ghrelin-GHSR pathway involve neutralization of circulating ghrelin by antibodies and RNA spiegelmers, antagonism of ghrelin receptor by its antagonists and inverse agonists, inhibition of ghrelin O-acyltransferase (GOAT), as well as potential pharmacological approach to decrease ghrelin synthesis and secretion. Conclusion: Various compounds targeting the ghrelin-GHSR system have shown promising efficacy for intervention of obesity and relevant metabolic disorders in animals and in vitro. Further clinical trials to validate their efficacy in human being are urgently needed.

G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro

2014 ◽  
Vol 306 (1) ◽  
pp. E28-E35 ◽  
Author(s):  
Zhi Gong ◽  
Makoto Yoshimura ◽  
Sayaka Aizawa ◽  
Reiko Kurotani ◽  
Jeffrey M. Zigman ◽  
...  
Keyword(s):  
G Protein ◽  
Cell Lines ◽  
G Protein Coupled Receptor ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Expression Levels ◽  
Ghrelin Secretion ◽  
G Protein Coupled

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced predominantly in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased immediately after feeding and that fasting-induced ghrelin release is controlled by the sympathetic nervous system. However, the mechanisms of plasma ghrelin decrement after feeding are poorly understood. Here, we studied the control of ghrelin secretion using ghrelin-producing cell lines and found that these cells express high levels of mRNA encoding G-protein coupled receptor 120 (GPR120). Addition of GW-9508 (a GPR120 chemical agonist) and α-linolenic acid (a natural ligand for GPR120) inhibited the secretion of ghrelin by ∼50 and 70%, respectively. However, the expression levels of preproghrelin and ghrelin O-acyltransferase (GOAT) mRNAs were not influenced by GW-9508. In contrast, the expression levels of prohormone convertase 1 were decreased significantly by GW-9508 incubation. Moreover, we observed that the inhibitory effect of GW-9508 on ghrelin secretion was blocked by a small interfering RNA (siRNA) targeting the sequence of GPR120. Furthermore, pretreatment with GW-9508 blocked the effect of the norepinephrine (NE)-induced ghrelin elevation in ghrelin cell lines. In addition, we showed that GW-9508 inhibited ghrelin secretion via extracellular signal-regulated kinase activity in ghrelin cell lines. Finally, we found that GW-9508 decreased plasma ghrelin levels in mice. These results suggest that the decrease of ghrelin secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric GPR120-expressing ghrelin cells.

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