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Diabetologia. 2014 Feb;57(2):383-91. doi: 10.1007/s00125-013-3096-5. Epub 2013 Nov 5.

The role of the transcription factor ETV5 in insulin exocytosis.

Author information

1
Department of Internal Medicine, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH, 45237, USA.

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 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.

PMID:
24190582
PMCID:
PMC3947344
DOI:
10.1007/s00125-013-3096-5
[Indexed for MEDLINE]
Free PMC Article

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