Expression of insulinoma-associated 2 (INSM2) in pancreatic islet cells is regulated by the transcription factors Ngn3 and NeuroD1

Authors

Tao Cai, National Institute of Dental and Craniofacial Research (NIDCR)
Xiang Chen, Wenzhou Medical University
Rennian Wang, Western UniversityFollow
Huan Xu, Fudan University
Yuhui You, Wenzhou Medical University
Tao Zhang, Children's Hospital of New Orleans
Michael S. Lan, Children's Hospital of New Orleans
Abner L. Notkins, National Institute of Dental and Craniofacial Research (NIDCR)

Document Type

Article

Publication Date

5-1-2011

Journal

Endocrinology

Volume

152

Issue

5

First Page

1961

Last Page

1969

URL with Digital Object Identifier

10.1210/en.2010-1065

Abstract

The insulinoma-associated 2 (Insm2) gene is a member of the Snail/Gfi1/Insm1 transcriptional repressor superfamily. However, little is known about how the expression of human INSM2 or mouse Insm2 in neuroendocrine tissues is regulated. Here we report the expression of INSM2/Insm2 in human fetal pancreas and mouse embryos, as well as adult pancreatic islets, and its regulation by two major islet transcription factors. Mutagenesis and chromatin immunoprecipitation analysis demonstrated that the proximal E-boxes of the mouse Insm2 promoter are directtargets of neurogenin3 and neurogenic differentiation1 (NeuroD1). Furthermore, wefound that endogenous Insm2 expression was activated in Ngn3/NeuroD1-transduced pancreatic epithelial duct cells. Our results suggest that Insm2 plays an important role in the differentiation cascade of Ngn3/NeuroD1 signaling in pancreatic islets. Copyright © 2011 by The Endocrine Society.