| First Author | Lim GE | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 7 | Pages | 2649-59 |
| PubMed ID | 27167773 | Mgi Jnum | J:239725 |
| Mgi Id | MGI:5829541 | Doi | 10.1210/en.2016-1016 |
| Citation | Lim GE, et al. (2016) Ywhaz/14-3-3zeta Deletion Improves Glucose Tolerance Through a GLP-1-Dependent Mechanism. Endocrinology 157(7):2649-59 |
| abstractText | 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, 14-3-3zeta, as a critical regulator of in vitro beta-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 (14-3-3zetaKO) exhibited elevated fasting insulin levels while maintaining normal beta-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 14-3-3zetaKO mice after an oral glucose gavage. This improvement in glucose tolerance was associated with significantly elevated fasting glucagon-like peptide-1 (GLP-1) levels. 14-3-3zeta 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 14-3-3zetaKO mice. When taken together these findings demonstrate novel roles of 14-3-3zeta in the regulation of glucose homeostasis and suggest that modulating 14-3-3zeta levels in intestinal L cells may have beneficial metabolic effects through GLP-1-dependent mechanisms. |
