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Deepali Gupta, Jen-Chieh Chuang, Bharath K Mani, Kripa Shankar, Juan A Rodriguez, Sherri Osborne-Lawrence, Nathan P Metzger, Jeffrey M Zigman
The ghrelin system is a key component of the mood and metabolic responses to chronic psychosocial stress. For example, circulating acyl-ghrelin rises in several rodent and human stress models, administered acyl-ghrelin induces antidepressant-like behavioral responses in mice, and mice with deleted ghrelin receptors (GHSRs) exhibit exaggerated depressive-like behaviors, changed eating behaviors, and altered metabolism in response to chronic stress. However, the mechanisms mediating stress-induced rises in ghrelin are unknown and ghrelin's antidepressant-like efficacy in the setting of chronic stress is incompletely characterized...
February 8, 2019: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Xingshen Sun, Yaling Yi, Bo Liang, Yu Yang, Nan He, Katie Larson Ode, Aliye Uc, Kai Wang, Katherine N Gibson-Corley, John F Engelhardt, Andrew W Norris
BACKGROUND: Insulin secretion is insufficient in cystic fibrosis (CF), even before diabetes is present, though the mechanisms involved remain unclear. Acyl-ghrelin (AG) can diminish insulin secretion and is elevated in humans with CF. METHODS: We tested the hypothesis that elevated AG contributes to reduced insulin secretion and hyperglycemia in CF ferrets. RESULTS: Fasting AG was elevated in CF versus non-CF ferrets. Similar to its effects in other species, AG administration in non-CF ferrets acutely reduced insulin, increased growth hormone, and induced hyperglycemia...
February 6, 2019: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Yao Lin, Zerong Liang, Liping He, Mengliu Yang, Dongfang Liu, Harvest F Gu, Hua Liu, Zhiming Zhu, Hongting Zheng, Ling Li, Gangyi Yang
BACKGROUND: Ghrelin modulates many physiological processes. However, the effects of intestinal ghrelin on hepatic glucose production (HGP) are still unclear. The current study was to explore the roles of intestinal ghrelin on glucose homeostasis and insulin signaling in the liver. METHODS: The system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-3 H] glucose as a tracer were used to analyze the effect of intestinal ghrelin...
January 25, 2019: Cell Communication and Signaling: CCS
Bing Wu, Yongling Liu, Fuyan Liu, Qing Deng, Jinglei Wang, Renwen Han, Dalei Zhang, Jiaxiang Chen, Jie Wei
Ghrelin(1-7)-NH2 is the active N-terminal hepta-peptide of ghrelin as an agonist at the ghrelin receptor GHS-R1α. The biological functions of ghrelin(1-7)-NH2 have not been well investigated. Therefore in this study, we were interested in exploring the effects and molecular mechanisms of ghrelin(1-7)-NH2 in pain modulation at the supraspinal level using the tail withdrawal test in mice. Intracerebroventricular (i.c.v.) injection of ghrelin(1-7)-NH2 (0.002, 0.02, 0.2 and 2 nmol/kg) induced a dose- and time-related antinociceptive effect...
December 29, 2018: Brain Research Bulletin
Brian C Small, Sylvie M A Quiniou, Hiroyuki Kaiya, Jacob W Bledsoe, Bryan Musungu
A novel third channel catfish growth hormone secretagogue (ghrelin) receptor, GHS-R3a, gene was characterized. Identification and analysis of the genomic organization of channel catfish GHS-R3a revealed differences in exon/intron structure relative to the previously published GHS-R1a and GHS-R2a sequences. Amino acid sequence alignment of catfish GHS-R3a with -R1a and -R2a revealed 48 and 52% sequence identity, respectively. Phylogenetic analysis predicted a new clade of GHS-R3a receptors found only in fish, with representation in the teleost infradivisions Osteoglossomorpha, Clupeomorpha, and Euteleostei...
November 21, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Junxian Ma, Xinbo Wang, Tingting Lv, Jie Liu, Ying Ren, Jinshan Zhang, Yan Zhang
Ghrelin is a circulating peptide hormone, which involved in promoting feeding and regulating energy metabolism in human and rodents. Abnormal synovial hyperplasia is the most important pathologic hallmark of rheumatoid arthritis (RA), which is characterised by tumor-like expansion. Existing studies indicated that there may exist some relation between the decreased ghrelin and the abnormally proliferating synovial cells in RA. Therefore, the aim of this study is to explore the apoptotic effects of ghrelin on MH7A synovial cells in vitro...
November 15, 2018: Biological & Pharmaceutical Bulletin
Xin-Tong Fan, Zhao Tian, Shi-Zhen Li, Ting Zhai, Jun-Li Liu, Rui Wang, Cai-Shun Zhang, Liu-Xin Wang, Jun-Hua Yuan, Yu Zhou, Jing Dong
Studies of nesfatin-1 in glucose metabolism have become a topic of interest recently, however, the specific receptor for nesfatin-1 has not yet been identified. Some studies hinted at a connection between nesfatin-1 and the ghrelin receptor, growth hormone secretagogue receptor. Therefore, we aimed to study the role of GHSR in the glycemic effects of nesfatin-1 as well as its downstream pathways. We employed C57/BL6 mice (wild type and GHSR knockout mice) eating a normal chow diet and a high fat diet in this study, and the experimental technique included western blot, real-time PCR, immunofluorescence and ELISA...
2018: Frontiers in Endocrinology
Michelle L Maugham, Inge Seim, Patrick B Thomas, Gabrielle J Crisp, Esha T Shah, Adrian C Herington, Laura S Gregory, Colleen C Nelson, Penny L Jeffery, Lisa K Chopin
PURPOSE: The ghrelin axis regulates many physiological functions (including appetite, metabolism, and energy balance) and plays a role in disease processes. As ghrelin stimulates prostate cancer proliferation, the ghrelin receptor antagonist [D-Lys3 ]-GHRP-6 is a potential treatment for castrate-resistant prostate cancer and for preventing the metabolic consequences of androgen-targeted therapies. We therefore explored the effect of [D-Lys3 ]-GHRP-6 on PC3 prostate cancer xenograft growth...
November 2, 2018: Endocrine
Mohamed Darwesh Morsy
This study investigated the effect of acylated ghrelin (AG) deficiency after sleeve gastrectomy (SG) or chronic administration in control and SG-indiuced rats on platelet function, coagulation, and fibrinolysis. Administration of AG (100 µg/kg, subcutaneously) to control or SG rats significantly inhibited platelets aggregation and lowered levels of Von-Willebrand factor (vWF), fibrinogen, and thromboxane B2. Concomitantly, it decreased circulatory levels and aortic expression levels of plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and increased the aortic expression of the endothelial nitric oxidase (eNOS)...
October 15, 2018: Archives of Physiology and Biochemistry
P J Torres, E M Luque, M F Ponzio, V Cantarelli, M Diez, S Figueroa, L M Vincenti, V P Carlini, A C Martini
The purpose of this study was to evaluate the intragestational role of ghrelin in offspring development and reproductive programming in a mouse model of ghrelin imbalance during pregnancy. Female mice were injected with ghrelin (supraphysiological levels: 4 nmol/animal/day), antagonist (endogenous ghrelin inhibition with (D-Lys3)GHRP-6, 6 nmol/animal/day) or vehicle (control = normal ghrelin levels) throughout the pregnancy. Parameters evaluated in litters were growth, physical, neurobiological and sexual development and, at adulthood, reproductive function...
October 1, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Milan M Fowkes, Tyler Lalonde, Lihai Yu, Savita Dhanvantari, Michael S Kovacs, Leonard G Luyt
The ghrelin receptor is a seven-transmembrane (7-TM) receptor known to have an increased level of expression in human carcinoma and heart failure. Recent work has focused on the synthesis of positron emission tomography (PET) probes designed to target and image this receptor for disease diagnosis and staging. However, these probes have been restricted to small-molecule quinalizonones and peptide derivatives of the endogenous ligand ghrelin. We describe the design, synthesis and biological evaluation of a series of 4-fluorobenzoylated growth hormone secretagogues (GHSs) derived from peptidic (GHRP-1, GHPR-2 and GHRP-6) and peptidomimetic (G-7039, [1-Nal4 ]G-7039 and ipamorelin) families in order to test locations for the insertion of fluorine-18 for PET imaging...
September 5, 2018: European Journal of Medicinal Chemistry
Mohammad Dallak
This study investigated the effect of sub-chronic administration of unacylated ghrelin (UAG) on steroidogenesis, sperm parameter, and reproductive function in lean and high fat diet (HFD)-induced obese male rats. Rats were divided into 4 groups (n = 12 each) as 1) Control-fed standard diets (STD): (10 kcal%), 2) STD + UAG (200 ng/kg, i.p.), 3) HFD obese: fed HFD (45 kcal%), and 4) HFD + UAG. Diet regimen was continued for 16 weeks after which normal saline as a vehicle or UAG was administered to desired groups for the next 4 weeks...
September 28, 2018: Systems Biology in Reproductive Medicine
Jun Wang, Lin He, Bahetiyaer Huwatibieke, Lingchao Liu, He Lan, Jing Zhao, Yin Li, Weizhen Zhang
Adipose tissue is hyper-vascularized. Vessels in adipose tissue not only supply nutrients and oxygen to nourish adipocytes, but also provide cytokines that regulate mass and function of adipose tissue. Understanding the fundamental mechanisms how vessels modulate adipocyte functions would provide new therapeutic options for treatment of metabolic disease and obesity. In recent years, researches about ghrelin are focused on glucose and lipid metabolism, but its effect on vascular function remains uncharacterized...
August 26, 2018: International Journal of Molecular Sciences
JinHong Jiang, YaLi Peng, XueYa Liang, Shu Li, Xin Chang, LongFei Li, Min Chang
Cortistatin-14 (CST-14), a recently discovered cyclic neuropeptide, can bind to all five cloned somatostatin receptors (SSTRs) and ghrelin receptor to exert its biological activities and co-exists with GABA within the cortex and hippocampus. However, the role of CST-14 in the control of depression processes is not still clarified. Here, we tested the behavioral effects of CST-14 in the in a variety of classical rodent models of depression [forced swimming test (FST), tail suspension test (TST) and novelty-suppressed feeding test]...
2018: Frontiers in Pharmacology
Magdalena Popławska, Agata Błażewicz
Growth hormone releasing peptides (GHRPs) are synthetic peptides with the ability to stimulate human growth hormone (hGH) secretion. Several GHRPs have been developed as drug candidates; however, only one of them, GHRP-2 (Pralmorelin), has received a clinical approval. Nevertheless, they are distributed on the black market and misused by cheating athletes, due to their performance-enhancing effects. Hence, GHRPs have been included in the World-Anti-Doping-Agency's Prohibited List as forbidden substances in sport...
July 27, 2018: Drug Testing and Analysis
Pedro Javier Torres, Eugenia Mercedes Luque, Marina Flavia Ponzio, Verónica Cantarelli, Marcela Diez, Silvia Figueroa, Laura Maria Vincenti, Valeria Paola Carlini, Ana Carolina Martini
The purpose of this study was to evaluate the intragestational role of ghrelin in offspring development and reproductive programming in a mouse model of ghrelin imbalance during pregnancy. Female mice were injected with ghrelin (supraphysiological levels: 4 nmol/animal/day), antagonist (endogenous ghrelin inhibition with (D-Lys3)GHRP-6, 6 nmol/animal/day) or vehicle (control=normal ghrelin levels) throughout the pregnancy. Parameters evaluated in litters were growth, physical, neurobiological, and sexual development and, at adulthood, reproductive function...
July 10, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Kazunori Kageyama, Satoru Sakihara, Wataru Kameda, Aya Sugiyama, Shinobu Takayasu, Ken Terui, Makoto Daimon
Thyrotropin (TSH)-producing adenomas are a rare cause of hyperthyroidism and are a type of functional pituitary adenoma. The diagnosis of TSH-producing adenoma is a challenging problem in clinical endocrinology. Since growth hormone-releasing peptide-2 (GHRP-2) fails to induce TSH secretion in normal subjects, the effect of GHRP-2 on TSH levels was therefore examined in patients with TSH-producing adenomas. A total of 5 patients (4 women and 1 man) referred to our departments for further evaluation of pituitary hormones were followed-up using the GHRP-2, TSH-releasing hormone (TRH), octreotide, and bromocriptine tests to examine and evaluate TSH secretory dynamics in TSH-producing adenomas...
October 29, 2018: Endocrine Journal
Kouichi Yamamoto, Yukihiro Isogai, Takayuki Ishida, Keisuke Hagihara
Teriparatide is clinically used for the treatment of osteoporosis; however, nausea is often observed in patients. Its insufficient control affects the ability to continue teriparatide therapy. Rikkunshi-To (RKT), a traditional Japanese herbal medicine, improves the gastrointestinal function via activation of the ghrelin-signaling system. We investigated the therapeutic effects of RKT on teriparatide-induced nausea in rats and the involvement of ghrelin in these effects. We previously reported that ovariectomized rats showed pica (kaolin ingestion), a behavior that can be used to assess nausea in rats, after the subcutaneous administration of teriparatide; thus, the behavior was used as an index of nausea...
June 2018: Journal of Pharmacological Sciences
Loïze Maréchal, Maximilien Laviolette, Amélie Rodrigue-Way, Baly Sow, Michèle Brochu, Véronique Caron, André Tremblay
Uncovering the biological role of nuclear receptor peroxisome proliferator-activated receptors (PPARs) has greatly advanced our knowledge of the transcriptional control of glucose and energy metabolism. As such, pharmacological activation of PPARγ has emerged as an efficient approach for treating metabolic disorders with the current use of thiazolidinediones to improve insulin resistance in diabetic patients. The recent identification of growth hormone releasing peptides (GHRP) as potent inducers of PPARγ through activation of the scavenger receptor CD36 has defined a novel alternative to regulate essential aspects of lipid and energy metabolism...
May 21, 2018: International Journal of Molecular Sciences
Oliver Krug, Andreas Thomas, Helle Malerød-Fjeld, Yvette Dehnes, Tim Laussmann, Ingo Feldmann, Albert Sickmann, Mario Thevis
Detecting agents allegedly or evidently promoting growth such as human growth hormone (GH) or growth hormone releasing peptides (GHRP) in doping controls has represented a pressing issue for sports drug testing laboratories. While GH is a recombinant protein with a molecular weight of 22 kDa, the GHRPs are short (3-6 amino acids long) peptides with GH releasing properties. The endogenously produced GH (22 kDa isoform) consists of 191 amino acids and has a monoisotopic molecular mass of 22,124 Da. Within this study, a slightly modified form of GH was discovered consisting of 192 amino acids carrying an additional alanine at the N-terminus, leading to a monoisotopic mass of 22,195 Da...
August 2018: Growth Hormone & IGF Research
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