A peptide triple agonist of GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors promotes glycemic control and weight loss.

Autor: Chichura KS; Department of Chemistry, Syracuse University, 111 College Place, Syracuse, NY, 13244, USA., Elfers CT; Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA., Salameh TS; Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA., Kamat V; Diabetes Research Institute and Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, 98195, USA., Chepurny OG; Department of Medicine, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA., McGivney A; Department of Chemistry, Syracuse University, 111 College Place, Syracuse, NY, 13244, USA., Milliken BT; Department of Chemistry, Syracuse University, 111 College Place, Syracuse, NY, 13244, USA., Holz GG; Department of Medicine, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA.; Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA., Applebey SV; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Hayes MR; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Sweet IR; Diabetes Research Institute and Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, 98195, USA., Roth CL; Seattle Children's Research Institute, 1900 Ninth Ave, Seattle, WA, 98101, USA. Christian.roth@seattlechildrens.org.; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, 98105, USA. Christian.roth@seattlechildrens.org., Doyle RP; Department of Chemistry, Syracuse University, 111 College Place, Syracuse, NY, 13244, USA. Rpdoyle@syr.edu.; Department of Medicine, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA. Rpdoyle@syr.edu.; Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA. Rpdoyle@syr.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jun 12; Vol. 13 (1), pp. 9554. Date of Electronic Publication: 2023 Jun 12.
DOI: 10.1038/s41598-023-36178-1
Abstrakt: Mechanisms underlying long-term sustained weight loss and glycemic normalization after obesity surgery include changes in gut hormone levels, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). We demonstrate that two peptide biased agonists (GEP44 and GEP12) of the GLP-1, neuropeptide Y1, and neuropeptide Y2 receptors (GLP-1R, Y1-R, and Y2-R, respectively) elicit Y1-R antagonist-controlled, GLP-1R-dependent stimulation of insulin secretion in both rat and human pancreatic islets, thus revealing the counteracting effects of Y1-R and GLP-1R agonism. These agonists also promote insulin-independent Y1-R-mediated glucose uptake in muscle tissue ex vivo and more profound reductions in food intake and body weight than liraglutide when administered to diet-induced obese rats. Our findings support a role for Y1-R signaling in glucoregulation and highlight the therapeutic potential of simultaneous receptor targeting to achieve long-term benefits for millions of patients.
(© 2023. The Author(s).)
Databáze: MEDLINE
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