{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:06:39Z","timestamp":1789452399842,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,7]],"date-time":"2018-10-07T00:00:00Z","timestamp":1538870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31071916, 81703102"],"award-info":[{"award-number":["31071916, 81703102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Laboratory Projects of Department of Education of Liaoning Province","award":["LZ2015044"],"award-info":[{"award-number":["LZ2015044"]}]},{"name":"Innovative Research Team Program of Department of Education of Liaoning Province","award":["LT2015011"],"award-info":[{"award-number":["LT2015011"]}]},{"name":"Scientific Research Program for Public Welfare of Liaoning Province","award":["20170022"],"award-info":[{"award-number":["20170022"]}]},{"name":"Foundation of China Medical University","award":["XZR20160022"],"award-info":[{"award-number":["XZR20160022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes is a metabolic disorder leading to many complications. The treatment of diabetes mainly depends on hypoglycemic drugs, often with side effects, which drive us to develop novel agents. AWRK6 was a peptide developed from the antimicrobial peptide Dybowskin-2CDYa in our previous study, and the availability of AWRK6 on diabetes intervention was unknown. Here, in vivo and in vitro experiments were carried out to investigate the effects of AWRK6 against diabetes. In diabetic mice, induced by high-fat diet followed by streptozocin (STZ) administration, the daily administration of AWRK6 presented acute and sustained hypoglycemic effects. The plasma insulin was significantly elevated by AWRK6 during an oral glucose tolerance test (OGTT). The relative \u03b2 cell mass in diabetic mice was increased by AWRK6 treatment. The body weight and food intake were remarkably reduced by AWRK6 administration. In the mouse pancreatic \u03b2 cell line Min6 cells, the intracellular calcium concentration was found to be enhanced under the treatment with AWRK6, and protein kinase A (PKA) inhibitor H-89 and Epac2 inhibitor HJC0350 represented inhibitory effects of the insulinotropic function of AWRK6. By FITC-AWRK6 incubation and GLP-1 receptor (GLP-1R) knockdown, AWRK6 proved to be a novel GLP-1R agonist. In addition, AWRK6 showed no toxicity in cell viability and membrane integrity in Min6 cells, and no hypoglycemia risk and no lethal toxicity in mice. In summary, AWRK6 was found as a novel agonist of GLP-1R, which could stimulate insulin secretion to regulate blood glucose and energy metabolism, via cAMP-calcium signaling pathway, without significant toxicity. The peptide AWRK6 might become a novel candidate for diabetes treatment.<\/jats:p>","DOI":"10.3390\/ijms19103053","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T10:44:53Z","timestamp":1538995493000},"page":"3053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["AWRK6, a Novel GLP-1 Receptor Agonist, Attenuates Diabetes by Stimulating Insulin Secretion"],"prefix":"10.3390","volume":"19","author":[{"given":"Qiuyu","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Science, Liaoning University, Shenyang 110036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Life Science, Liaoning University, Shenyang 110036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Life Science, Liaoning University, Shenyang 110036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Science, Liaoning University, Shenyang 110036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifan","family":"Miao","sequence":"additional","affiliation":[{"name":"School of Life Science, Liaoning University, Shenyang 110036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province, Liaoning University, Shenyang 110036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-7742","authenticated-orcid":false,"given":"Dianbao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cohen Sabban, E.N., Puchulu, F.M., and Cusi, K. 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