Metabolic effects of combined glucagon receptor antagonism and glucagon-like peptide-1 receptor agonism in high fat fed mice

Ablation of glucagon receptor (GCGR) signalling is a potential treatment option for diabetes, whilst glucagon-like peptide-1 (GLP-1) receptor agonists are clinically approved for both obesity and diabetes. There is a suggestion that GCGR blockade enhances GLP-1 secretion and action, whilst GLP-1 rec...

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Veröffentlicht in:Biochimie 2022-08, Vol.199, p.60-67
Hauptverfasser: Franklin, Zara J., Lafferty, Ryan A., Flatt, Peter R., McShane, Laura M., O'Harte, Finbarr P.M., Irwin, Nigel
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Sprache:eng
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Zusammenfassung:Ablation of glucagon receptor (GCGR) signalling is a potential treatment option for diabetes, whilst glucagon-like peptide-1 (GLP-1) receptor agonists are clinically approved for both obesity and diabetes. There is a suggestion that GCGR blockade enhances GLP-1 secretion and action, whilst GLP-1 receptor activation is known to inhibit glucagon release, implying potential for positive interactions between both therapeutic avenues. The present study has examined the ability of sustained GCGR antagonism, using desHis1Pro4Glu9-glucagon, to augment the established benefits of the GLP-1 mimetic, exendin-4, in high fat fed (HFF) mice. Twice-daily injection of desHis1Pro4Glu9-glucagon, exendin-4 or a combination of both peptides to groups of HFF mice for 10 days had no impact on body weight or energy intake. Circulating blood glucose and glucagon concentrations were significantly (P 
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2022.04.005