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Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist.

Grunddal KV, Diep TA, Petersen N, Tough IR, Skov LJ, Liu L, Buijink JA, Mende F, Jin C, Jepsen SL, Sørensen LME, Achiam MP, Strandby RB, Bach A, Hartmann B, Frimurer TM, Hjorth SA, Bouvier M, Cox H, Holst B

Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA.

Obesity is a complex disease associated with a high risk of co-morbidities. Gastric bypass surgery, an invasive procedure with low patient eligibility, is currently the most effective intervention that achieves sustained weight loss. This beneficial effect is attributed to alterations in gut hormone signaling. An attractive alternative is to pharmacologically mimic the effects of bariatric surgery by targeting several gut hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed in the gastrointestinal tract has been shown to mediate ghrelin signaling and control appetite, food intake and energy homeostasis, but the broader effect on gut hormones is largely unknown. A potent and efficaous GPR39 agonist (Cpd1324) was recently discovered, but the in vivo function was not addressed. Here we studied the efficacy of the GPR39 agonist, Cpd1324, on metabolism and gut hormone secretion.

Mol Metab 2021:101207.

Pubmed ID: 33711555

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