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

Authors: Yeom, SY  Kim, GH  Kim, CH  Jung, HD  Kim, SY  Park, JY  Pak, YK  Rhee, DK  Kuang, SQ  Xu, J  Han, DJ  Song, DK  Lee, JW  Lee, KU  Kim, SW 
Citation: Yeom SY, etal., Mol Cell Biol. 2006 Jun;26(12):4553-63.
Pubmed: (View Article at PubMed) PMID:16738321
DOI: Full-text: DOI:10.1128/MCB.01412-05

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 beta-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 beta-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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CRRD Object Information
CRRD ID: 9590126
Created: 2014-11-13
Species: All species
Last Modified: 2014-11-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.