Showing papers on "Growth hormone secretagogue published in 2020"
TL;DR: It is shown that the accessory protein MRAP2 altered GHSR1a signaling by inhibiting its constitutive activity, as well as by enhancing its G protein–dependent signaling and blocking the recruitment and signaling of β-arrestin in response to ghrelin.
Abstract: Ghrelin is a hormone secreted by the stomach during fasting periods and acts through its receptor, the growth hormone secretagogue 1a (GHSR1a), to promote food intake and prevent hypoglycemia. As such, GHSR1a is an important regulator of energy and glucose homeostasis and a target for the treatment of obesity. Here, we showed that the accessory protein MRAP2 altered GHSR1a signaling by inhibiting its constitutive activity, as well as by enhancing its G protein-dependent signaling and blocking the recruitment and signaling of β-arrestin in response to ghrelin. In addition, the effects of MRAP2 on the Gαq and β-arrestin pathways were independent and involved distinct regions of MRAP2. These findings may have implications for the regulation of ghrelin function in vivo and the role of MRAP2 in energy homeostasis. They also show that accessory proteins can bias signaling downstream of GPCRs in response to their endogenous agonist.
36 citations
TL;DR: A review of the current literature concerning ghrelin’s physiological roles in energy and glucose homeostasis concludes that further research in humans is required before gh Relin can be indicated as a therapeutic target in obesity or diabetes.
Abstract: Ghrelin is a peptide hormone that is primarily released from the stomach. It is best known for its role in appetite initiation. However, evidence also suggests that ghrelin may play a much wider role in energy homeostasis and glucose metabolism. It is known that exogenous ghrelin exerts an orexigenic signal via growth hormone secretagogue receptors in the arcuate nucleus of the hypothalamus. However, blocking ghrelin signalling in the arcuate nucleus does not decrease feeding. Evidence now proposes that an alternative pathway for ghrelin's action is via the vagus nerve. Furthermore, it has been suggested that ghrelin signalling is an important physiological regulator of body adiposity and energy storage. Ghrelin also seems to be important in controlling glucose metabolism through action in the pancreatic islets of Langerhans, representing a promising novel therapeutic target in diabetes treatment. Despite these findings, further research in humans is required before ghrelin can be indicated as a therapeutic target in obesity or diabetes. This review summarises the current literature concerning ghrelin's physiological roles in energy and glucose homeostasis.
17 citations
19 Apr 2020
TL;DR: The results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats, and co-localizes with insulin in the secretory granules of pancreaticBeta cells and enhances insulin production.
Abstract: Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24–51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10−6 M and 10−12 M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.
14 citations
TL;DR: It might be that decreased circulating UAG/AG, rather than UAG or AG alone, were involved in IR and liver lipid accumulation in NAFLD.
Abstract: Objective(s): Ghrelin is a brain-gut peptide involved in substance and energy metabolism To confirm the hypothesis that ghrelin might be involved in non-alcoholic fatty liver disease (NAFLD), a rat NAFLD model was established and the changes of ghrelin were exploredMaterials and Methods: The rats were divided into control and NAFLD groups The rats in the NAFLD group were fed a high-fat–high-cholesterol (HFHC) diet for 8 weeks Total ghrelin (TG), acylated ghrelin (AG), unacylated ghrelin (UAG), and hypothalamic AG and its receptor GHSR-1a expression were detected using ELISA, RIA, RT-PCR, and Western blot, respectivelyResults: Plasma UAG, TG, and the ratio of UAG to AG (UAG/AG) decreased, while protein and mRNA expression of hypothalamic AG and growth hormone secretagogue receptor-1a (GHSR-1a) increased in NAFLD (P<001) Plasma UAG and UAG/AG were negatively associated with homeostatic model assessment insulin resistance (HOMA-IR), while AG positively correlated with HOMA-IR (R2=06510, P=0005; R2=08520, P=0000; R2=05617, P=0013, respectively) Plasma UAG, TG and UAG/AG negatively correlated with serum LDL-C or hepatic triglycerides (TGs) (R2=07733, P=0001; R2=06930, P=0003; R2=06042, P=0008; R2=07046, P=0002; R2=06722, P=0004; R2=05124, P=0020, respectively) Hypothalamic AG and GHSR-1a positively correlated with HOMA-IR or hepatic TGs (R2=05116, P=0020; R2=05220, P=0018; R2=06074, P=0008; R2=05127, P=0020, respectively)Conclusion: It might be that decreased circulating UAG/AG, rather than UAG or AG alone, were involved in IR and liver lipid accumulation in NAFLD Acylated ghrelin might induce IR and promote liver lipid accumulation via a central mechanism involved in the hypothalamus
8 citations
TL;DR: Results suggest that HBO administration improved glucose metabolism in a STZ-induced T1DM mouse model, and involves improved insulin-release, glucose-sensing and regulation of hepatic glycogen storage, an observation that was also likely dependent on the ghrelin signalling system.
Abstract: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder for which the only effective therapy is insulin replacement. Hyperbaric oxygen (HBO) therapy has demonstrated potential in improving hyperglycemia and as a treatment option for T1DM. Ghrelin and HBO have been previously reported to exert proliferative, anti‑apoptotic and anti‑inflammatory effects in pancreatic cells. The present study investigated the mechanism underlying HBO‑ and ghrelin system‑mediated regulation of glucose metabolism. Male C57BL/6 mice were intraperitoneally injected with streptozotocin (STZ; 150 mg/kg) to induce T1DM before the diabetic mice were randomly assigned into the T1DM and T1DM + HBO groups. Mice in the T1DM + HBO group received HBO (1 h; 100% oxygen; 2 atmospheres absolute) daily for 2 weeks. Significantly lower blood glucose levels and food intake were observed in mice in the T1DM + HBO group. Following HBO treatment, islet β‑cell area were increased whereas those of α‑cell were decreased in the pancreas. In addition, greater hepatic glycogen storage in liver was observed, which coincided with higher pancreatic glucose transporter 2 (GLUT2) expression levels and reduced hepatic GLUT2 membrane trafficking. There were also substantially higher total plasma ghrelin concentrations and gastric ghrelin‑O‑acyl transferase (GOAT) expression levels in mice in the T1DM + HBO group. HBO treatment also abolished reductions in pancreatic GOAT expression levels in T1DM mice. Additionally, hepatic growth hormone secretagogue receptor‑1a levels were found to be lower in mice in the T1DM + HBO group compared with those in the T1DM group. These results suggest that HBO administration improved glucose metabolism in a STZ‑induced T1DM mouse model. The underlying mechanism involves improved insulin‑release, glucose‑sensing and regulation of hepatic glycogen storage, an observation that was also likely dependent on the ghrelin signalling system.
7 citations
TL;DR: GF could activate hypothalamic AMPK-autophagy and suppress POMC expression via gastrointestinal hormones to ameliorate hypercatabolism compared with JF, which suggested that GF may be the preferred route of EN in endotoxemic rats.
Abstract: Background Hypercatabolism is associated with increased infectious rates and mortality in critically ill patients. Enteral nutrition (EN) is usually used to counteract hypercatabolism. However, the impact of different routes of EN on hypercatabolism remains unknown. Here, we compared the impact of gastric feeding (GF) and jejunal feeding (JF) on gastrointestinal hormones and hypercatabolism, which is associated with hypothalamic adenosine 5'-monophosphate-activated protein kinase (AMPK)-autophagy-proopiomelanocortin (POMC). Methods Sixty adult male Sprague-Dawley rats were divided into 5 groups: Sham and lipopolysaccharide (LPS) groups fed a standard chow diet, a pair-fed group that was a subset of saline-treated rats pair-fed with the LPS group, and LPS + JF and LPS + GF groups (received EN via jejunal and gastric tube, respectively, for 3 days [100 kcal/kg/d]). Hypercatabolism was measured by insulin resistance, muscle protein synthesis, and atrophy. Serum gastrointestinal hormones, hypothalamic ghrelin, growth hormone secretagogue receptor-1α (GHS-R1α), and AMPK-autophagy-POMC markers were also detected. Results GF increased serum total, acylated, desacylated, and hypothalamic ghrelin and decreased glucagon-like peptide-1 (GLP-1). But no effect on pancreatic polypeptide (PYY) and hypothalamic GHS-R1α was observed. JF showed no effect on hypothalamic ghrelin, GHS-R1α, and serum total, acylated, and desacylated ghrelin and even further aggravated GLP-1 and PYY. GF could effectively augment hypothalamic AMPK-autophagy-POMC and hypercatabolism. However, JF showed no effect on hypothalamic AMPK-autophagy-POMC and hypercatabolism. Conclusions GF could activate hypothalamic AMPK-autophagy and suppress POMC expression via gastrointestinal hormones to ameliorate hypercatabolism compared with JF, which suggested that GF may be the preferred route of EN in endotoxemic rats.
7 citations