The role of the transcription factor ETV5 in insulin exocytosis

Ruth Gutierrez-Aguilar, Dong Hoon Kim, Marina Casimir, Xiao Qing Dai, Paul T. Pfluger, Jongsun Park, April Haller, Elizabeth Donelan, Jisoo Park, David D'Alessio, Stephen C. Woods, Patrick E. MacDonald, Randy J. Seeley

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)383-391
Number of pages9
JournalDiabetologia
Volume57
Issue number2
DOIs
Publication statusPublished - 2014 Feb

Keywords

  • Beta cell
  • ETV5
  • Genome-wide association study
  • Glucose homeostasis
  • Insulin exocytosis
  • Insulin secretion
  • Insulin sensitivity
  • Transcription factor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Gutierrez-Aguilar, R., Kim, D. H., Casimir, M., Dai, X. Q., Pfluger, P. T., Park, J., Haller, A., Donelan, E., Park, J., D'Alessio, D., Woods, S. C., MacDonald, P. E., & Seeley, R. J. (2014). The role of the transcription factor ETV5 in insulin exocytosis. Diabetologia, 57(2), 383-391. https://doi.org/10.1007/s00125-013-3096-5