Regulation of Insulin Secretion and β-Cell Mass by Activating Signal Cointegrator 2
- Author(s)
- 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
- Keimyung Author(s)
- Song, Dae Kyu
- Department
- Dept. of Physiology (생리학)
- Journal Title
- Molecular and Celluar Biology
- Issued Date
- 2006
- Volume
- 26
- Issue
- 12
- 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 -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 -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.
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