scholarly journals Therapeutic effects of acylated ghrelin-specific receptor GHS-R1a antagonist in islet transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoshi Chinen ◽  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Masafumi Nakamura ◽  
Shohta Kodama
Keyword(s):  
Islet Transplantation ◽  
Therapeutic Effects ◽  
Β Cells ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Therapeutic Outcomes ◽  
Severe Diabetes ◽  
Ghrelin Receptors ◽  
Mouse Islets ◽  
Regulation Of Growth

AbstractIslet transplantation is a type of cellular replacement therapy for severe diabetes that is limited by compromising effect on engrafted islets. Trials aiming to improve the function of transplanted islets have also been challenging. This study attempted to elucidate whether regulation of growth hormone secretagogue receptor-1a (GHS-R1a), one of the ghrelin receptors, improve the therapeutic effects of islet transplantation using [D-Lys3]-GHRP-6 (DLS), a specific GHS-R1a antagonist. The therapeutic effects of DLS were assessed in terms of the expression/production of endocrine genes/proteins, insulin-releasing function under glucose stimulation of mouse islets, and outcomes of syngeneic murine islet transplantation with systemic DLS administration. DLS treatment promoted insulin production and suppressed somatostatin production, suggesting that cancelation of the binding between ghrelin and GHS-R1a on β or δ cells improved insulin expression. DLS also promoted the glucose-dependent insulin-releasing function of β cells. However, the therapeutic effect of DLS in islet transplantation was fractional. In conclusion, the GHS-R1a antagonist showed preferable effects in improving the therapeutic outcomes of islet transplantation, including the promotion of insulin-releasing function.

scholarly journals Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance

2006 ◽  
Vol 290 (6) ◽  
pp. G1289-G1297 ◽  
Author(s):  
Galina Burdyga ◽  
Andrea Varro ◽  
Rod Dimaline ◽  
David G. Thompson ◽  
Graham J. Dockray
Keyword(s):  
Receptor Expression ◽  
Afferent Neurons ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Nodose Ganglia ◽  
Melanin Concentrating Hormone ◽  
Ghrelin Receptors ◽  
Vagal Afferent ◽  
Immunohistochemical Studies

Intact vagal afferent neurons are required for the satiety effects of the intestinal hormone cholecystokinin (CCK) and the orexigenic effects of the gastric regulatory peptide ghrelin. In this study, we examined the localization of ghrelin receptors in nodose ganglia and their function in regulating the expression of other orexigenic receptors, notably cannabinoid (CB)-1 and melanin-concentrating hormone (MCH)-1 receptors. With the use of RT-PCR, transcripts corresponding to both functional [growth hormone secretagogue receptor (GHS-R)1a] and truncated forms (GHS-R1b) of the ghrelin receptor were detected in rat nodose ganglia. There was no difference in expression between rats fed ad libitum or fasted for up to 48 h. Immunohistochemical studies using antibodies directed at GHS-R1a revealed expression in over 75% of neurons also expressing CCK-1 receptors in the mid- and caudal regions of the ganglion. There was also expression in human nodose ganglia. In fasted rats in which CB-1 and MCH-1 receptor expression was increased, administration of ghrelin prevented the downregulation by refeeding. We conclude that the actions of CCK and ghrelin are mediated by a common population of vagal afferent neurons. Ghrelin may act to limit the action of CCK in depressing expression of CB-1 and MCH-1 receptors and other receptors.

Circulating messenger for neuroprotection induced by molecular hydrogen

2019 ◽  
Vol 97 (10) ◽  
pp. 909-915 ◽  
Author(s):  
Mami Noda ◽  
Yuya Uemura ◽  
Yusuke Yoshii ◽  
Taichi Horita ◽  
Shota Takemi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drinking Water ◽  
Nerve Injury ◽  
Molecular Hydrogen ◽  
Disease Model ◽  
Chronic Administration ◽  
The Body ◽  
Therapeutic Effects ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

Molecular hydrogen (H2) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H2was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H2in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H2. It suggests indirect signaling of H2and gastrointestinal tract is involved. Indirect effects of H2could be tested by giving H2water only before nerve injury, as preconditioning. For example, preconditioning of H2for certain a period (∼7 days) in Parkinson’s disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H2in drinking water induces ghrelin production and release from the stomach via β1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood–brain barrier, activates its receptor, growth-hormone secretagogue receptor. H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H2and raise intriguing preventive and therapeutic options using H2.

scholarly journals Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System

2021 ◽  
Vol 22 (19) ◽  
pp. 10571
Author(s):  
Grzegorz Ginter ◽  
Piotr Ceranowicz ◽  
Zygmunt Warzecha
Keyword(s):  
Growth Hormone ◽  
Digestive System ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Current Data ◽  
The Body ◽  
Therapeutic Effects ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Risk Of Cancer

Ghrelin is an endogenous ligand for the ghrelin receptor, previously known as the growth hormone secretagogue receptor. This hormone is mainly produced by endocrine cells present in the gastric mucosa. The ghrelin-producing cells are also present in other organs of the body, mainly in the digestive system, but in much smaller amount. Ghrelin exhibits a broad spectrum of physiological effects, such as stimulation of growth hormone secretion, gastric secretion, gastrointestinal motility, and food intake, as well as regulation of glucose homeostasis and bone formation, and inhibition of inflammatory processes. This review summarizes the recent findings concerning animal and human data showing protective and therapeutic effects of ghrelin in the gut, and also presents the role of growth hormone and insulin-like growth factor-1 in these effects. In addition, the current data on the possible influence of ghrelin on the carcinogenesis, its importance in predicting the risk of developing gastrointestinal malignances, as well as the potential usefulness of ghrelin in the treatment of cancer, have been presented.

Surface Modified Nanoparticulate Carriers for the Targeted Treatment of Breast Cancer

2015 ◽  
Vol 8 (1) ◽  
pp. 2698-2714
Author(s):  
Neeraj Mishra ◽  
Tejinder Singh ◽  
Nidhi ◽  
Supandeep Singh Hallan ◽  
Veerpal Kaur
Keyword(s):  
Breast Cancer ◽  
Tumor Targeting ◽  
Lipid Nanoparticles ◽  
Targeted Treatment ◽  
Therapeutic Effects ◽  
Target Drug Delivery ◽  
Target Drug ◽  
Therapeutic Outcomes ◽  
Lipid Nanocarriers ◽  
Surface Modified

Breast cancer left overs one of the greatest common metastasis disease in females. Advanced diagnostic devices and better understanding of tumour biology can extend the better therapeutic outcomes. Nanotechnology is a tool that helps in cancer diagnosis and treatment therapy. Many nanocarriers such as solid lipid nanoparticles, magnetic nanoparticles, nanocrystals, nanogels, nano-lipid nanocarriers, biodegradable nanoparticles, liposomes, and dendrimers are introduced to improve the therapeutic efficacy of antineoplastic agents. Surface modified target drug delivery system has the potential to increase the therapeutic effects and also reduce the cytotoxicity of breast cancer. Different approaches have been explored for treatment of breast cancer. This review describes the recent advances in the development of nanocarriers used for the targeted treatment of breast cancer. It also focuses on etiology, risk factor and conventional therapy of breast cancer. KEYWORDS: Breast Cancer; Nano-carriers; Tumor Targeting; Ligands; Receptor.

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

scholarly journals Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice

2020 ◽  
Vol 119 ◽  
pp. 104718
Author(s):  
María Paula Cornejo ◽  
Franco Barrile ◽  
Daniela Cassano ◽  
Julieta Paola Aguggia ◽  
Guadalupe García Romero ◽  
...  
Keyword(s):  
Growth Hormone ◽  
High Fat Diet ◽  
Dopamine Neurons ◽  
High Fat ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ad Libitum
Sign in / Sign up

Export Citation Format

Share Document