Regulation of insulin secretion and β-cell mass by activating signal cointegrator 2

Seon Yong Yeom, Geun Hyang Kim, Chan Hee Kim, Heun Don Jung, So Yeon Kim, Joong Yeol Park, Youngmi Kim Pak, Dong Kwon Rhee, Shao Qing Kuang, Jianming Xu, Duck Jong Han, Dae Kyu Song, Jae Woon Lee, Ki Up Lee, Seung Whan Kim

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2 +/- mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/- mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2 +/- islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

Original languageEnglish (US)
Pages (from-to)4553-4563
Number of pages11
JournalMolecular and cellular biology
Volume26
Issue number12
DOIs
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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