Journal ArticleDOI
Liver-Expressed Antimicrobial Peptide 2 antagonizes the insulinostatic effect of ghrelin in rat isolated pancreatic islets.
Morgane Bayle,Sylvie Peraldi-Roux,Guillaume Gautheron,Gérard Cros,Catherine Oiry,Jérémie Neasta +5 more
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TLDR
In this paper, Liver-Expressed Antimicrobial Peptide 2 (LEAP2) was recognized as an endogenous G-protein coupled receptor (GPCR) ligand that blocks ghrelin-induced actions.Abstract:
Background The hormone ghrelin is the endogenous agonist of the G-protein coupled receptor (GPCR) termed growth-hormone secretagogue receptor (GHSR). Ghrelin inhibits glucose-stimulated insulin secretion by activating pancreatic GHSR. Recently, Liver-Expressed Antimicrobial Peptide 2 (LEAP2) was recognized as an endogenous GHSR ligand that blocks ghrelin-induced actions. Nonetheless, the effect of LEAP2 on glucose-stimulated insulin secretion from pancreatic islets is unknown. Objectives We aimed at exploring the activity of LEAP2 on glucose-stimulated insulin secretion. Methods Islets of Langerhans isolated from rat pancreas were exposed to glucose in the presence or in the absence of LEAP2 and ghrelin and then insulin secretion was assayed. Results LEAP2 did not modulate glucose-stimulated insulin secretion. However, LEAP2 blocked the insulinostatic action of ghrelin. Conclusion Our data show that LEAP2 behaves as an antagonist of pancreatic GHSR.read more
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Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes
TL;DR: In this paper , the authors focus on describing how feeding-induced crosstalk between hepatokines, including Adropin, Manf, Leap2 and Pcsk9, and metabolic organs (e.g. brain, heart, pancreas, and adipose tissue) affects metabolic disorders, thus revealing a novel approach for both controlling and managing of Type 2 diabetes as a promising medication.
Journal ArticleDOI
Design and Characterization of a Triazole-Based Growth Hormone Secretagogue Receptor Modulator Inhibiting the Glucoregulatory and Feeding Actions of Ghrelin.
Sylvie Peraldi-Roux,Morgane Bayle,Céline M'Kadmi,Marjorie Damian,Justine Vaillé,Gimena Fernandez,Maria Paula Cornejo,Jacky Marie,Jean-Louis Banères,Khoubaib Ben Haj Salah,Jean-Alain Fehrentz,Sonia Cantel,Mario Perello,Séverine Denoyelle,Catherine Oiry,Jérémie Neasta +15 more
TL;DR: In this paper , a triazole-derived modulator of growth hormone secretagogue receptor (GHSR) is proposed to mitigate several pathological features associated with eating and metabolic disorders.
Journal ArticleDOI
Why Search for Alternative GPCR Agonists?
Jean A. Boutin,Jérôme Leprince +1 more
TL;DR: In this paper , the authors try to rationalize these fields of research, since they proved to be very successful over the years, with receptor pharmacology populated with dozens of alternative agonists, particularly to bioaminergic receptors, and to a lesser extent to peptidergic ones.
References
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Journal ArticleDOI
Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets
Michael R. DiGruccio,Alex M. Mawla,Cynthia J. Donaldson,Glyn M. Noguchi,Joan Vaughan,Christopher Cowing-Zitron,Talitha van der Meulen,Mark O. Huising +7 more
TL;DR: The findings illustrate the power of the approach to resolve some of the long-standing conundrums with regard to the rich feedback that occurs within the islet that is integral to islet physiology and therefore highly relevant to diabetes.
Journal ArticleDOI
The Homeostatic Force of Ghrelin.
TL;DR: The current understanding of the regulatory mechanisms of the ghrelin system in energy metabolism and cellular homeostasis and its clinical trials are highlighted and future studies of gh Relin will further elucidate how the stomach regulates systemicHomeostasis.
Journal ArticleDOI
LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor
Xuecai Ge,Hong Yang,Maria A. Bednarek,Hadas Galon-Tilleman,Peirong Chen,Michael Chen,Joshua S. Lichtman,Yan Wang,Olivier Dalmas,Yiyuan Yin,Hui Tian,Lutz Jermutus,Joseph Grimsby,Cristina M. Rondinone,Anish Konkar,Daniel D. Kaplan +15 more
TL;DR: The discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous antagonist of GHSR is reported, revealing a mechanism for fine-tuning ghrelin action in response to changing environmental conditions.
Journal ArticleDOI
LEAP2 changes with body mass and food intake in humans and mice
Bharath K. Mani,Nancy Puzziferri,Nancy Puzziferri,Zhenyan He,Juan A. Rodriguez,Juan A. Rodriguez,Sherri Osborne-Lawrence,Sherri Osborne-Lawrence,Nathan P. Metzger,Nathan P. Metzger,Navpreet Chhina,Bruce D. Gaylinn,Michael O. Thorner,E. Louise Thomas,Jimmy D. Bell,Kevin W. Williams,Anthony P. Goldstone,Jeffrey M. Zigman +17 more
TL;DR: It is predicted that the plasma LEAP2/acyl-gh Relin molar ratio may be a key determinant modulating acyl-ghrelin activity in response to body mass, feeding status, and blood glucose.
Journal ArticleDOI
N-Terminal Liver-Expressed Antimicrobial Peptide 2 (LEAP2) Region Exhibits Inverse Agonist Activity toward the Ghrelin Receptor.
Céline M'Kadmi,Agustina Cabral,Franco Barrile,Julien Giribaldi,Sonia Cantel,Marjorie Damian,Sophie Mary,Séverine Denoyelle,Sébastien Dutertre,Sylvie Péraldi-Roux,Jérémie Neasta,Catherine Oiry,Jean-Louis Banères,Jacky Marie,Mario Perello,Jean-Alain Fehrentz +15 more
TL;DR: It is found that both LEAP2 and its N-terminal part behave as inverse agonists of GHSR and as competitive antagonists of ghrelin-induced inositol phosphate production and calcium mobilization.
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