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A novel glucose stimulated network: IA-2 beta, miR-153 and its target genes

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • L Abuhatzira
  • W Mandemakers
  • H Xu
  • T Cai
  • B De Strooper
  • AL Notkins


Islet antigen 2 (IA-2) and IA-2beta, two of the major auto-antigens in type 1 diabetes, are transmembrane proteins in dense core secretory vesicles (DCV) of neuroendocrine cells. Disruption of these proteins leads to impaired secretion of insulin and neurotransmitters. Interestingly, the microRNA gene miR-153 is embedded in intron 19 of both IA-2 and IA-2beta and is encoded in two copies (miR-153-1 and miR-153-2, respectively). We demonstrate that expression of mir-153-2 and IA-2beta in rodents is co-regulated in both brain tissue and pancreatic islets, as demonstrated by a strong reduction of miR-153 expression levels in IA-2beta knockout mice. Moreover, stimulation of the mouse insulinoma cell line (MIN6) by glucose significantly increases both IA-2beta and miR-153 expression. Using bioinformatics approaches we identified targets of miR-153 that correlate with IA-2beta localization and function. We found increased expression of several of these target genes in the islets and brain tissues of IA-2beta mice. Next, we over expressed miR-153-2 in MIN6 cells using either a mimic or glucose stimulation and found reduced expression of target genes. These findings point to an involvement of IA-2beta, mir-153 and its target genes in a regulatory network triggered by glucose which is potentially relevant to diabetes and neurodegenerative diseases.

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