{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:10:08Z","timestamp":1784758208717,"version":"3.55.0"},"reference-count":45,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:p>Multiple signaling pathways mediate the actions of metabolic hormones to control glucose homeostasis, but the proteins that coordinate such networks are poorly understood. We previously identified the molecular scaffold protein, 14-3-3\u03b6, as a critical regulator of in vitro \u03b2-cell survival and adipogenesis, but its metabolic roles in glucose homeostasis have not been studied in depth. Herein, we report that Ywhaz gene knockout mice (14-3-3\u03b6KO) exhibited elevated fasting insulin levels while maintaining normal \u03b2-cell responsiveness to glucose when compared with wild-type littermate controls. In contrast with our observations after an ip glucose bolus, glucose tolerance was significantly improved in 14-3-3\u03b6KO mice after an oral glucose gavage. This improvement in glucose tolerance was associated with significantly elevated fasting glucagon-like peptide-1 (GLP-1) levels. 14-3-3\u03b6 knockdown in GLUTag L cells elevated GLP-1 synthesis and increased GLP-1 release. Systemic inhibition of the GLP-1 receptor attenuated the improvement in oral glucose tolerance that was seen in 14-3-3\u03b6KO mice. When taken together these findings demonstrate novel roles of 14-3-3\u03b6 in the regulation of glucose homeostasis and suggest that modulating 14-3-3\u03b6 levels in intestinal L cells may have beneficial metabolic effects through GLP-1-dependent mechanisms.<\/jats:p>","DOI":"10.1210\/en.2016-1016","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T17:00:47Z","timestamp":1462986047000},"page":"2649-2659","source":"Crossref","is-referenced-by-count":35,"title":["Ywhaz\/14-3-3\u03b6 Deletion Improves Glucose Tolerance Through a GLP-1-Dependent Mechanism"],"prefix":"10.1210","volume":"157","author":[{"given":"Gareth E.","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Cellular and Physiological Sciences (G.E.L., M.P., J.D.J.), University of British Columbia, Vancouver, BC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Piske","sequence":"first","affiliation":[{"name":"Department of 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