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Heppner, K.M.* ; Piechowski, C.L.* ; Müller, A.* ; Ottaway, N.* ; Sisley, S.* ; Smiley, D.L.* ; Habegger, K.M.* ; Pfluger, P.T. ; DiMarchi, R.* ; Biebermann, H.* ; Tschöp, M.H. ; Sandoval, D.A.* ; Perez-Tilve, D.*

Both acyl and des-acyl ghrelin regulate adiposity and glucose metabolism via CNS ghrelin receptors.

Diabetes 63, 122-131 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Ghrelin receptors (GHSRs) in the central nervous system (CNS) mediate hyperphagia and adiposity induced by acyl ghrelin (AG). Evidence suggests that des-acyl ghrelin (dAG) has biological activity through GHSR independent mechanisms. We combined in vitro and in vivo approaches to test possible GHSR-mediated biological activity of dAG. Both AG (100nM) and dAG (100nM) significantly increased IP3 formation in HEK-293 cells transfected with human GHSR. As expected, intracerebroventricular (icv) infusion of AG in mice increased fat mass (FM), in comparison with the saline-infused controls. Icv-dAG also increased FM at the highest dose tested (5 nmol/day). Chronic icv infusion of AG or dAG increased glucose-stimulated insulin secretion (GSIS). Subcutaneously infused AG regulated FM and GSIS in comparison to saline-infused control mice, whereas dAG failed to regulate these parameters even with doses that were efficacious when delivered icv. Furthermore, icv-dAG failed to regulate FM and induce hyperinsulinemia in GHSR deficient (Ghsr-/-) mice. In addition, a hyperinsulinemic-euglycemic clamp suggests that icv-dAG impairs glucose clearance without affecting endogenous glucose production. Taken together, these data demonstrate that dAG is an agonist of GHSR and regulates body adiposity and peripheral glucose metabolism through a CNS GHSR-dependent mechanism.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 63, Issue: 1, Pages: 122-131 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)