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Dive into the research topics where Emanuela Arvat is active.

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Featured researches published by Emanuela Arvat.


Journal of Endocrinological Investigation | 2000

Preliminary evidence that Ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans

Emanuela Arvat; L. Di Vito; Fabio Broglio; Mauro Papotti; Giampiero Muccioli; Carlos Dieguez; Felipe F. Casanueva; Romano Deghenghi; F. Camanni; Ezio Ghigo

An endogenous ligand for the GH secretagogue-receptor (GHS-R) has been recently purified from rat and human stomach and named Ghrelin. It has been demonstrated that Ghrelin specifically stimulates GH secretion from rat pituitary cells in culture as well as in rats in vivo. In this preliminary study, in 4 normal adults [age (mean±SE): 28.6±3.5 yr; body mass index (BMI): 22.3±2.1 kg/m2] we administered 1.0 μg/kg Ghrelin or GHRH-29 to compare their GH-releasing activities in humans. In all subjects Ghrelin induced a prompt, marked and long-lasting increase in circulating GH levels (peak: 107.9±26.1 μg/l; AUC: 6503.1±1632.7 μg/l/h). The GH response to Ghrelin was clearly higher (p<0.05) than that after GHRH (peak: 22.3±4.5 μg/l; AUC: 1517.5±338.4 μg/l/h). In conclusion, this preliminary study shows that Ghrelin exerts a strong stimulatory effect on GH secretion in humans releasing more GH than GHRH.


Clinical Endocrinology | 2005

Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor

Ezio Ghigo; Fabio Broglio; Emanuela Arvat; Mauro Maccario; Mauro Papotti; Giampiero Muccioli

Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor type 1a (GHS‐R1a). Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also nonendocrine actions that are explained by the widespread distribution of ghrelin and GHS‐R expression. The likely existence of GHS‐R subtypes and evidence that the neuroendocrine actions, but not all the other actions, of ghrelin depend on its acylation in serine‐3 revealed a system whose complexity had not been completely explored by studying synthetic GHS. Ghrelin secretion is mainly regulated by metabolic signals and, in turn, the modulatory action of ghrelin on the control of food intake and energy metabolism seems to be among its most important biological actions. However, according to a recent study, ghrelin‐null mice are neither anorectics nor dwarfs and this evidence clearly depicts a remarkable difference from leptin null mice. Nevertheless, the original and fascinating story of ghrelin, as well as its potential pathophysiological implications in endocrinology and internal medicine, is not definitively cancelled by these data as GHS‐R1a null aged mice show significant alterations in body composition and growth, in glucose metabolism, cardiac function and contextual memory. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, there are several open questions awaiting an answer. How many ghrelin receptor subtypes exist? Is ghrelin ‘the’ or just ‘a’ GHS‐R ligand? That is, are there other natural GHS‐R ligands? Is there a functional balance between acylated and unacylated ghrelin forms, potentially with different actions? Within the next few years suitable answers to these questions will probably be found, making it possible to gain a better knowledge of ghrelins potential clinical perspectives.


Endocrine | 2001

Biologic activities of growth hormone secretagogues in humans

Ezio Ghigo; Emanuela Arvat; Roberta Giordano; Fabio Broglio; Laura Gianotti; Mauro Maccario; Gianni Bisi; Andrea Graziani; Mauro Papotti; Giampiero Muccioli; Romano Deghenghi; F. Camanni

Growth hormone secretagogues (GHSs) are synthetic peptidyl and nonpeptidyl molecules with strong, dose-dependent, and reproducible growth hormone (GH)-releasing activity even after oral administration. GHSs release GH via actions on specific receptors (GHS-R) at the pituitary and, mainly, at the hypothalamic levels. GHSs likely act as functional somatostatin antagonists and meantime enhance the activity of GH-releasing hormone (GHRH)-secreting neurons. The GH-releasing effect of GHSs is independent of gender but undergoes marked age-related variations. Estrogens play a major role in enhancing the GH response to GHSs at puberty, which GHRH hypoactivity, somatostatinergic hyperactivity and impaired activity of the putative GHS-like ligand and receptors probably explain the reduced GH-releasing effect of GHSs in aging. The activity of GHSs is not fully specific for GH. Their slight prolactin-releasing activity probably comes from direct pituitary action. In physiological conditions, the ACTH-releasing activity of GHSs is dependent on central actions; a direct action on GHS-R in pituitary ACTH-secreting tumors likely explains the peculiar ACTH and cortisol hyperresponsiveness to GHSs in Cushing disease. GHSs have specific receptor subtypes in other central and peripheral endocrine and nonendocrine tissues mediating GH-independent biologic activities. GHSs influence sleep pattern, stimulated food intake, and have cardiovascular activities. GHs have specific binding in normal and neoplastic follicular derived human thyroid tissue and inhibit the proliferation of follicular-derived neoplastic cell lines. The discovery of ghrelin, a 28 amino acid peptide synthesized in the stomach but also in other tissues, has opened new fascinating perspectives of research in this field.


Journal of Endocrinological Investigation | 2003

Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans

Fabio Broglio; Andrea Benso; Cristina Gottero; Flavia Prodam; C. Gauna; L. Filtri; Emanuela Arvat; A. J. van der Lely; Romano Deghenghi; Ezio Ghigo

Ghrelin, a 28-amino acid peptide predominantly produced by the stomach, displays strong GH-releasing activity mediated by the GH secretagogue (GHS)-receptor (GHS-R) type 1a at the hypothalamus-pituitary level. Ghrelin and synthetic GHS also possess other GH-independent peripheral endocrine and non-endocrine activities via the activation of peripheral GHS-R subtypes. In rats in vivo non-acylated ghrelin has been reported devoid of any endocrine activity; however, in vitro, it has been shown as effective as ghrelin in exerting anti-proliferative activity on tumor cell lines. The aim of the present study was to clarify whether non-acylated human ghrelin shares some of the endocrine activities of its acylated form in humans. To this goal, the effects of acylated or non-acylated ghrelin (1.0 μg/kg iv at 0 min) on GH, PRL, ACTH, F, insulin and glucose levels were studied in two different testing sessions in 7 normal young volunteers (age [mean±SE]: 24.3±1.7 yr; BMI: 21.5±0.9 kg/m2). The effects of placebo administration were also studied. The administration of acylated ghrelin induced prompt and marked increase in circulating GH levels (AUC: 5452.4±904.9 μg*min/l; p<0.01 vs placebo) and significant increase in PRL (1273.5±199.7 μg*min/l; p<0.01 vs placebo), ACTH (4482.7±954.4 pg*min/ml; p<0.01 vs placebo) and F levels (15985.0±1141.9 μg*min/l; p<0.01 vs placebo). Its administration was also followed by decrease in insulin levels (1448.67±137.9 mU*min/l; p<0.05 vs placebo) that was coupled with an increase in plasma glucose levels (10974.2±852.5 mg*min/dl; p<0.05 vs placebo). The administration of non-acylated ghrelin and that of placebo did not induce any change in the hormonal parameters or in glucose levels. In conclusion, this study shows that in humans nonacylated ghrelin does not possess the pituitaric and pancreatic endocrine activities of human ghrelin octanoylated in Serine 3.


Endocrine | 2001

Growth hormone-releasing hormone combined with arginine or growth hormone secretagogues for the diagnosis of growth hormone deficiency in adults.

Ezio Ghigo; Gianluca Aimaretti; Emanuela Arvat; F. Camanni

Insulin-induced hypoglycemia (ITT) is currently the “gold-standard” test for the diagnosis of adult growth hormone deficiency (GHD). ITT is often contraindicated, however, particularly in conditions that are also common in patients with suspected GHD. Used alone, GH-releasing hormone (GHRH) has no diagnostic value owing to within-subject variability and the inability to distinguish GHD from normal subjects. When combined with arginine, however, GHRH becomes a potent and reproducible test, which is unaffected by gender and aging, showing excellent specificity. The GHRH+ arginine (ARG) test distinguishes GHD patients from normal subjects and is at least as sensitive as ITT, provided that appropriate cutoff limits are considered. Its reliability for retesting GHD has also been demonstrated. The GHRH+ARG test can also be performed in a shorter procedure, resulting in potential for cost reduction. Synthetic GH secretagogues (GHSs) possess a strong and reproducible GH-releasing effect and synergize with GHRH. The combination of GHRH and a peptidyl GHS, such as hexarelin or GH-releasing peptide-6, has recently been shown as another reliable test for the diagnosis of adult GHD, again provided that the cutoff limit is appropriate to the potency of the test. Thus, GHRH combined with either arginine or GHS is a potential tool for the diagnosis of adult GHD.


Hormone Research in Paediatrics | 2003

Endocrine and non-endocrine actions of ghrelin.

Fabio Broglio; Cristina Gottero; Emanuela Arvat; Ezio Ghigo

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amounts were detected in bowel, pancreas, kidneys, the immune system, placenta, testes, pituitary, and hypothalamus. Ghrelin displays strong growth hormone (GH)-releasing action mediated by the activation of the so-called GH secretagogue (GHS) receptor (GHS-R) type 1a. GHS-R are concentrated in the hypothalamus-pituitary unit but are also distributed in other central and peripheral tissues. Apart from the potent GH-releasing action, ghrelin has other actions including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, influence on exocrine and endocrine pancreatic function as well as on glucose metabolism, cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system. The discovery of ghrelin opened many new perspectives of research in neuroendocrinology and metabolism, and even also in other fields of internal medicine as gastroenterology, immunology, oncology and cardiology. The possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact is obviously suggested and is receiving great attention.


Frontiers in Neuroendocrinology | 1998

Growth Hormone-Releasing Peptides and Their Analogs

F. Camanni; Ezio Ghigo; Emanuela Arvat

Growth hormone-releasing peptides (GHRPs) are a series of hepta (GHRP-1)- and hexapeptides (GHRP-2, GHRP-6, Hexarelin) that have been shown to be effective releasers of GH in animals and humans. More recently, a series of nonpeptidyl GH secretagogues (L-692,429, L-692,585, MK-0677) were discovered using GHRP-6 as a template. Some cyclic peptides as well as penta-, tetra-, and pseudotripeptides have also been described. This review summarizes recent developments in our understanding of the GHRPs, as well as the current nonpeptide pharmacologic analogs. GHRPs and their analogs have no structural homology with GHRH and act via specific receptors present at either the pituitary or the hypothalamic level. The GHRP receptor has recently been cloned and it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. Although the exact mechanism of action of GHRPs has not been fully established, there is probably a dual site of action on both the pituitary and the hypothalamus, possibly involving regulatory factors in addition to GHRH and somatostatin. Moreover, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. The marked GH-releasing activity of GHRPs is reproducible and dose-related after intravenous, subcutaneous, intranasal, and even oral administration. The GH-releasing effect of GHRPs is the same in both sexes, but undergoes age-related variations. It increases from birth to puberty and decreases in aging. The GH-releasing activity of GHRPs is synergistic with that of GHRH and not affected by opioid receptor antagonists, while it is only blunted by inhibitory influences that are known to nearly abolish the effect of GHRH, such as neurotransmitters, glucose, free fatty acids, glucocorticoids, rhGH, and even exogenous somatostatin. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states, such as acromegaly, anorexia nervosa, and hyperthyroidism. On the other hand, GHRPs and their analogs have been reported to be effective in idiopathic short stature, in some situations of GH deficiency, in obesity, and in hypothyroidism, while in patients with pituitary stalk disconnection and in Cushings syndrome the somatotrope responsiveness to GHRPs is almost absent. A potential role in the treatment of short stature, aging, catabolic states, and dilated cardiomyopathy has been envisaged.


Clinical Endocrinology | 2006

Effect of protracted treatment with rosiglitazone, a PPARgamma agonist, in patients with Cushing's disease.

Francesca Pecori Giraldi; Carla Scaroni; Emanuela Arvat; Martina De Martin; Roberta Giordano; Nora Albiger; Adriana A. S. Leao; Andreea Picu; Franco Mantero; Francesco Cavagnini

Objective  Cushings disease, hypercortisolism due to a pituitary ACTH‐secreting tumour, is a highly morbid illness as yet without effective medical therapy. Recent studies have demonstrated that peroxisome proliferator‐activated receptor gamma (PPARγ) agonists effectively suppress ACTH secretion in a murine tumoral corticotroph cell line, but the few studies conducted so far in patients with ACTH‐secreting pituitary adenomas have yielded variable results.


Neuroendocrinology | 1991

Arginine reinstates the somatotrope responsiveness to intermittent growth hormone-releasing hormone administration in normal adults.

Ezio Ghigo; Emanuela Arvat; F. Valente; Mario Nicolosi; G. M. Boffano; M. Procopio; J. Bellone; Mauro Maccario; E. Mazza; F. Camanni

It is well known that in normal adults the growth hormone (GH) response to GH-releasing hormone (GHRH) is inhibited by previous administration of the neurohormone. In 7 healthy volunteers (age 20-34 years) we studied the GH responses to two consecutive GHRH boluses (1 microgram/kg i.v. every 120 min) alone or coadministered with arginine (30 g i.v. over 30 min). The GH response to the first GHRH bolus (area under the curve, mean +/- SEM: 506.3 +/- 35.1 micrograms/l/h) was higher (p = 0.0001) than that to the second one (87.1 +/- 14.6 micrograms/l/h). The latter response was clearly increased (p = 0.0001) by coadministering arginine (980.5 +/- 257.5 micrograms/l/h). When every GHRH bolus was combined with arginine a marked potentiation of GH response to both boluses was found. However, the second combined administration of arginine and GHRH induced a GH increase which was lower compared to the first one (p = 0.016). In conclusion, our results show that arginine potentiates the GHRH-induced GH secretion preventing the lessening of somatotrope responsiveness to the neurohormone alone. As there is evidence that this phenomenon is due to an enhanced somatostatin release, these findings give further evidence of a somatostatin-suppressing effect of arginine.


Clinical Endocrinology | 2002

The GH-releasing effect of ghrelin, a natural GH secretagogue, is only blunted by the infusion of exogenous somatostatin in humans.

Lidia Di Vito; Fabio Broglio; Andrea Benso; Cristina Gottero; Flavia Prodam; Mauro Papotti; Giampiero Muccioli; Carlos Dieguez; Felipe F. Casanueva; Romano Deghenghi; Ezio Ghigo; Emanuela Arvat

objective Ghrelin, a 28‐amino‐acid peptide purified from the stomach and showing a unique structure with an n‐octanoyl ester at the serine 3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS‐R). Ghrelin strongly stimulates GH secretion in both animals and humans, showing a synergistic effect with GH‐releasing hormone (GHRH) but no interaction with synthetic GHS. However, the activity of ghrelin as well as that of non‐natural GHS is not fully specific for GH; ghrelin also induces a stimulatory effect on lactotroph and corticotroph secretion, at least in humans.

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