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@article{Jones:2022:10.1111/dom.14794,
author = {Jones, B and Burade, V and Akalestou, E and Manchanda, Y and Ramchunder, Z and Carrat, G and Nguyen-Tu, M-S and Marchetti, P and Piemonti, L and Leclerc, I and Thennati, R and Vilsboll, T and Thorens, B and Tomas, A and Rutter, GA},
doi = {10.1111/dom.14794},
journal = {Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics},
pages = {2090--2101},
title = {In vivo and in vitro characterization of GL0034, a novel long-acting glucagon-like peptide-1 receptor agonist},
url = {http://dx.doi.org/10.1111/dom.14794},
volume = {24},
year = {2022}
}

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TY  - JOUR
AB  - AimsTo describe the in vitro characteristics and antidiabetic in vivo efficacy of the novel glucagon-like peptide-1 receptor agonist (GLP-1RA) GL0034.Materials and MethodsGlucagon-like peptide-1 receptor (GLP-1R) kinetic binding parameters, cyclic adenosine monophosphate (cAMP) signalling, endocytosis and recycling were measured using HEK293 and INS-1832/3 cells expressing human GLP-1R. Insulin secretion was measured in vitro using INS-1832/3 cells, mouse islets and human islets. Chronic administration studies to evaluate weight loss and glycaemic effects were performed in db/db and diet-induced obese mice.ResultsCompared to the leading GLP-1RA semaglutide, GL0034 showed increased binding affinity and potency-driven bias in favour of cAMP over GLP-1R endocytosis and β-arrestin-2 recruitment. Insulin secretory responses were similar for both ligands. GL0034 (6 nmol/kg) led to at least as much weight loss and lowering of blood glucose as did semaglutide at a higher dose (14 nmol/kg).ConclusionsGL0034 is a G protein-biased agonist that shows powerful antidiabetic effects in mice, and may serve as a promising new GLP-1RA for obese patients with type 2 diabetes.
AU  - Jones,B
AU  - Burade,V
AU  - Akalestou,E
AU  - Manchanda,Y
AU  - Ramchunder,Z
AU  - Carrat,G
AU  - Nguyen-Tu,M-S
AU  - Marchetti,P
AU  - Piemonti,L
AU  - Leclerc,I
AU  - Thennati,R
AU  - Vilsboll,T
AU  - Thorens,B
AU  - Tomas,A
AU  - Rutter,GA
DO  - 10.1111/dom.14794
EP  - 2101
PY  - 2022///
SN  - 1462-8902
SP  - 2090
TI  - In vivo and in vitro characterization of GL0034, a novel long-acting glucagon-like peptide-1 receptor agonist
T2  - Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics
UR  - http://dx.doi.org/10.1111/dom.14794
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000826738800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14794
UR  - http://hdl.handle.net/10044/1/103696
VL  - 24
ER  -

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