The Use of Ghrelin and Ghrelin Receptor Agonists as a Treatment for Animal Models of Disease: Efficacy and Mechanism

DeBoer, Mark D.

doi:10.2174/138161212803216951

Cited by 21 publications

(7 citation statements)

References 228 publications

(326 reference statements)

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“…This could indicate clinical applications for patients with other gastrointestinal motility disorders 41 . Although relamorelin has been shown to induce feeding and weight gain in multiple animal studies, 42‐45 weight changes in the phase 2 trials were small and not considered clinically relevant. To date, it remains unclear whether the 10 µg dose of relamorelin increases appetite in diabetic gastroparesis patients.…”

Section: Discussionmentioning

confidence: 99%

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Camilleri

Lembo

McCallum

et al. 2020

Aliment Pharmacol Ther

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Background: Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials. Aim:To assess the safety and tolerability of relamorelin across phase 2 trials. Methods: Safety assessments in patients aged 18-75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double-blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1-and 2-week, singleblind placebo run-ins.Results: Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment-emergent AE (TEAE). TEAE-related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose-related (P < 0.0001 and P = 0.0043, respectively). Conclusions:Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients.

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Section: Discussionmentioning

confidence: 99%

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Camilleri

Lembo

McCallum

et al. 2020

Aliment Pharmacol Ther

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“…This uremic malnutrition is associated with high morbidity, poor quality of life and increased mortality rates. The ghrelin is now under trial in animals and human to be used as treatment to stimulate appetite in ESRD patients [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Fetuin-A and Ghrelin Levels in Children with End Stage Renal Disease and the Effect of a Single Hemodialysis Session on Them

Shouman

Ismail

Badr

et al. 2015

Open Access Maced J Med Sci

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BACKGROUND:Fetuin-A and ghrelin have been implicated in cardiovascular diseases and mortality among end stage renal disease patients. The exact mechanisms have not been fully elucidated. There is robust data supporting an association between ghrelin and various cardiovascular conditions, and some common processes such as inflammation, oxidative stress, and endoplasmic reticulum stress have been implicated.AIM:This study was conducted to assay serum fetuin-A and ghrelin in chronic renal failure pediatric patients and to study changes in their level that may occur after a single hemodialysis.MATERIAL AND METHODS:Forty nine pediatric patients suffering from ESRD on maintenance hemodialysis (HD), 20 patients with chronic renal failure (CRF) not on dialysis and 35 healthy subjects as control group were included. The mean age of the study population was 10.58 ± 3.94, 10.62 ± 3.24 and 10.61 ± 3.97 years respectively. Serum fetuin-A and plasma acyl ghrelin levels were measured by using ELISA method.RESULTS:The present study revealed that predialysis serum fetuin-A level was significantly increased in pediatric HD patients compared with the normal population, while ghrelin levels were significantly reduced. Furthermore, serum levels of fetuin-A decreased significantly after a single HD session.CONCLUSION:Our study concluded that fetuin-A and acyl ghrelin may play a role in inflammatory process among HD pediatric patients which may account for cardiovascular insults and mortality but their use as biochemical markers among ESRD pediatric patients have limitations due to wide fluctuations.

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“…Perhaps not surprisingly, ghrelin is also elevated in cachexia . Exogenous ghrelin has shown promise with respect to promoting food intake and increased lean body mass in rodent models of cachexia .…”

Section: Ghrelin Regulation Of Glucose Metabolism Under Special Condimentioning

confidence: 99%

Ghrelin regulation of glucose metabolism

Gray

Page

Tong

2019

J Neuroendocrinology

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| INTRODUC TI ONSubsequent to its discovery in 1999, 1 ghrelin has been increasingly recognised for its role in diverse biological functions. Ghrelin stimulates growth hormone and adrenocorticotrophic hormone secretion, increases appetite and nutrient intake, decreases mean arterial blood pressure and augments cardiac output, enhances gut motility and gastric acid secretion, influences energy expenditure, affects learning and memory, and contributes to the hedonic aspects of food. 2,3 Ghrelin also impacts glucose metabolism both during typical fasting and fed states and at times of stress. For example, during starvation, ghrelin is essential for maintaining glucose homeostasis. 4-7 Although the ability of ghrelin to regulate glucose metabolism is widely accepted, the mechanisms by which it achieves these effects remain to be fully clarified. Ghrelin-induced lipolysis and counter regulatory hormone release is well recognised, 8-10 although only recently has its modulation of insulin release via pancreatic islet δ-cells 11,12 and a role in stimulating the secretion of other gastrointestinal hormones been identified. 10,13 This review focuses on the effects of ghrelin on glucose metabolism by summarising in vitro, rodent and human studies, at the same time as highlighting recent discoveries (Figure 1). Throughout the review, we use "acyl ghrelin" and "ghrelin" interchangeably and explicitly state studies reporting desacyl ghrelin or total ghrelin findings. Funding informationNational Institute of Diabetes and Digestive and Kidney Diseases: T32DK007012 to S.M.G., R01DK097550 to J.T Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are implicated in the regulation of glucose metabolism via direct actions in the pancreatic islet, as well as peripheral insulin-sensitive tissues and the brain. Although many studies have explored the role of ghrelin in glucose tolerance and insulin secretion, a complete mechanistic understanding remains to be clarified. This review highlights the local expression and function of ghrelin and GHSR1a in pancreatic islets and how this axis may modulate insulin secretion from pancreatic β-cells. Additionally, we discuss the effect of ghrelin on in vivo glucose metabolism in rodents and humans, as well as the metabolic circumstances under which the action of ghrelin may predominate. K E Y W O R D Sghrelin, glucose tolerance, insulin, insulin secretion

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The Use of Ghrelin and Ghrelin Receptor Agonists as a Treatment for Animal Models of Disease: Efficacy and Mechanism

Cited by 21 publications

References 228 publications

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Fetuin-A and Ghrelin Levels in Children with End Stage Renal Disease and the Effect of a Single Hemodialysis Session on Them

Ghrelin regulation of glucose metabolism

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