| First Author | Gutierrez-Aguilar R | Year | 2014 |
| Journal | Diabetologia | Volume | 57 |
| Issue | 2 | Pages | 383-91 |
| PubMed ID | 24190582 | Mgi Jnum | J:207688 |
| Mgi Id | MGI:5559385 | Doi | 10.1007/s00125-013-3096-5 |
| Citation | Gutierrez-Aguilar R, et al. (2014) The role of the transcription factor ETV5 in insulin exocytosis. Diabetologia 57(2):383-91 |
| abstractText | AIMS/HYPOTHESIS: Genome-wide association studies have revealed an association of the transcription factor ETS variant gene 5 (ETV5) with human obesity. However, its role in glucose homeostasis and energy balance is unknown. METHODS: Etv5 knockout (KO) mice were monitored weekly for body weight (BW) and food intake. Body composition was measured at 8 and 16 weeks of age. Glucose metabolism was studied, and glucose-stimulated insulin secretion was measured in vivo and in vitro. RESULTS: Etv5 KO mice are smaller and leaner, and have a reduced BW and lower fat mass than their wild-type controls on a chow diet. When exposed to a high-fat diet, KO mice are resistant to diet-induced BW gain. Despite a greater insulin sensitivity, KO mice have profoundly impaired glucose tolerance associated with impaired insulin secretion. Morphometric analysis revealed smaller islets and a reduced beta cell size in the pancreatic islets of Etv5 KO mice. Knockdown of ETV5 in an insulin-secreting cell line or beta cells from human donors revealed intact mitochondrial and Ca(2+) channel activity, but reduced insulin exocytosis. CONCLUSION/INTERPRETATION: This work reveals a critical role for ETV5 in specifically regulating insulin secretion both in vitro and in vivo. |
