Format

Send to

Choose Destination
Mol Cell Endocrinol. 2016 Jan 5;419:83-91. doi: 10.1016/j.mce.2015.10.002. Epub 2015 Oct 9.

The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus.

Author information

1
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
2
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark.
3
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
4
Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Pediatrics, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Center for Non-coding RNA in Technology and Health, University of Copenhagen, Denmark. Electronic address: flemming.pociot.01@regionh.dk.

Abstract

The study aimed to explore the role of ERBB3 in type 1 diabetes (T1D). We examined whether genetic variation of ERBB3 (rs2292239) affects residual β-cell function in T1D cases. Furthermore, we examined the expression of ERBB3 in human islets, the effect of ERBB3 knockdown on apoptosis in insulin-producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351) was found to be expressed in human islets. ERBB3 was expressed and down-regulated by pro-inflammatory cytokines in human islets and INS-1E cells; knockdown of ERBB3 in INS-1E cells decreased basal and cytokine-induced apoptosis. Our data suggests an important functional role of ERBB3 and its potential regulators in the β-cells and may constitute novel targets to prevent β-cell destruction in T1D.

KEYWORDS:

Apoptosis; Beta cell; CTCF; ERBB3; Type 1 diabetes; lncRNAs

PMID:
26450151
DOI:
10.1016/j.mce.2015.10.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center