Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis

Ariyasu, Hiroyuki; Iwakura, Hiroshi; Yukawa, Naoichiro; Murayama, Toshinori; Yokode, Masayuki; Tada, Harue; Yoshimura, Kenichi; Teramukai, Satoshi; Itô, Tatsuya; Shimizu, Akira; Yonezawa, Atsushi; Kangawa, Kenji; Mimori, Tsuneyo; Akamizu, Takashi

doi:10.1507/endocrj.ej14-0088

Cited by 24 publications

(14 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The genetically engineered mouse models with modified ghrelin systems that were used in these studies have significantly contributed to our knowledge of physiological importance of ghrelin. On the basis of the findings obtained from these mice and from pharmacological studies, small-scale clinical trials have been performed to assess the utility of ghrelin for the treatment of various disorders including anorexia nervosa [115], cancer cachexia [116,117], GI disorders [95,97,108], and aging-related disorders [119]. In order to make progress toward the clinical application of ghrelin for these diseases, long-term and largescale clinical trials and the further basic researches are needed.…”

Section: Discussionmentioning

confidence: 99%

“…The physiological role of ghrelin in GI motility is still controversial. Several studies reported that an administration of ghrelin accelerates gastric emptying and improves GI symptoms in patients with GI disorders due to systemic sclerosis [108], diabetic neuropathy [95], or post-vagotomy gastroparesis [97]. Although these trials were small cohort studies, their results suggest that ghrelin may have therapeutic potential for the treatment of GI dysmotility.…”

Section: Disclosuresmentioning

confidence: 99%

See 1 more Smart Citation

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system [Review]

Ariyasu

Akamizu

2015

Endocr J

Self Cite

View full text Add to dashboard Cite

Abstract. Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R or ghrelin receptor), is a 28-amino acid acylated peptide mainly produced in the stomach. The pharmacological administration of ghrelin is known to exert diverse effects, such as stimulating GH secretion, promoting food intake, and increasing adiposity. In recent years, genetically engineered mouse models have provided important insights into the physiology of various hormones. In this review, we discuss current knowledge regarding the physiological significance of ghrelin on the basis of studies using genetically engineered mouse models with modifications in the ghrelin system. Key word: GhrelinGHRELIN, an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R or ghrelin receptor), is a 28-amino acid acylated peptide [1]. Acyl-modification of ghrelin is essential for binding to ghrelin receptor, and is mediated by the membrane-bound ghrelin O-acyltransferase (GOAT) [2,3]. Ghrelin is mainly produced in the stomach, but is also expressed in the upper intestinal tract, pancreas, pituitary, and hypothalamus [1,4,5]. By contrast, the ghrelin receptor is expressed in the anterior pituitary and hypothalamus, suggesting that ghrelin/GHS-R signaling is involved in energy homeostasis and GH release [6][7][8]. Indeed, peripheral administration of ghrelin induces multiple effects, such as stimulating GH secretion, promoting food intake, and increasing adiposity [1,[9][10][11][12]. Using more sensitive PCR techniques, expression of ghrelin receptor has also been identified in the stomach, small intestine, pancreas, ventricular myocardium, aorta, adipose tissue, and lymphocytes [13][14][15]. The wide distribution of ghrelin and its receptor suggests that ghrelin might play a range of physiological roles.In order to investigate the physiological significance of hormones, genetically engineered mouse models have been widely utilized, and these models are also used as preclinical tools for exploring the novel therapeutic approaches for human disease. In this review, we discuss an outline of the physiological roles of ghrelin on the basis of research using genetically engineered mouse models, such as ghrelin-null, ghrelin receptor-null, ghrelin o-acyltransferase-null, and ghrelin-overexpressing mice. Secretion of GhrelinDate et al. reported that ghrelin-producing cells are X/A-like cells that account for about 20% of the endocrine cell population in rat and human oxyntic glands [16,17]. Ghrelin mRNA is most abundant in the stomach, and plasma ghrelin levels in totally gastrectomized patients were reduced to 35% of those in normal subjects, indicating that the stomach is a major source of circulating ghrelin [4]. Earlier studies revealed that circulating ghrelin levels reflect both acute and chronic energy status. In the acute phase, plasma ghrelin levels increase before meal and decrease after meal [4,[18][19][20]. In the chronic phase, plasma ghrelin levels are negatively correlated with BMI; for example, they ar...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Disclosuresmentioning

confidence: 99%

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system [Review]

Ariyasu

Akamizu

2015

Endocr J

Self Cite

View full text Add to dashboard Cite

show abstract

“…Octreotide does not seem to have an effect on gastric emptying or gastroparetic symptoms [60] . A placebo-controlled crossover study of infusion with the gastricderived prokinetic hormone ghrelin [61] in 10 patients with systemic sclerosis showed an acceleration of gastric emptying (53 minutes saline vs 43 minutes ghrelin) [62] , raising the potential for ghrelin analogues as therapy. Jejunal feeding can be considered in situations in which there is symptomatic delay in gastric emptying in the presence of normal small bowel transit [63] : this treatment and parenteral nutrition will be discussed in detail later.…”

Section: Vomiting and Abdominal Painmentioning

confidence: 99%

Current management of the gastrointestinal complications of systemic sclerosis

Emmanuel

2016

Nat Rev Gastroenterol Hepatol

View full text Add to dashboard Cite

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation.

show abstract

“…The gastric emptying rate was accelerated with ghrelin, but symptoms of post-prandial satiety did not change. No serious adverse events were reported [48]. In another article, Sallam et al systematically assessed the use of complementary alternative medicine use in SSc.…”

Section: Gastrointestinalmentioning

confidence: 99%

Systemic sclerosis

Young

Khanna

2015

Current Opinion in Rheumatology

View full text Add to dashboard Cite

Purpose of review To review pharmacologic and non-pharmacologic therapies in the treatment of systemic sclerosis (SSc) from 2011 to 2014 through a systematic review. Recent Findings Our systematic review identifies randomized controlled trials (RCT), meta-analyses, systematic reviews, case series and observational studies which support organ based therapy with known immunosuppressive agents, novel agents, and hematopoietic stem cell transplantation (HSCT), and also includes non-pharmacologic therapies improving visceral and physical function. Summary SSc is an orphan autoimmune disorder with significant morbidity and mortality. Although there has been significant progress over the years in therapeutic options for SSc, the mainstays of treatment are organ based and primarily symptom management. Our systematic review of the last 4 years of treatment emphasizes known treatment strategies already in practice, but also identifies new therapeutic approaches with additional biologic agents and HSCT.

show abstract

Clinical effects of ghrelin on gastrointestinal involvement in patients with systemic sclerosis

Cited by 24 publications

References 39 publications

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system [Review]

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system [Review]

Current management of the gastrointestinal complications of systemic sclerosis

Systemic sclerosis

Contact Info

Product

Resources

About