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Insulin-like growth factor binding protein-3 is a novel mediator of apoptosis in insulin-secreting cells.

Authors: Shim, ML  Levitt Katz, LE  Davis, J  Dotzler, WC  Cohen, P  Ferry RJ, JR 
Citation: Shim ML, etal., Growth Horm IGF Res. 2004 Jun;14(3):216-25.
Pubmed: (View Article at PubMed) PMID:15125883
DOI: Full-text: DOI:10.1016/j.ghir.2003.12.009

Insulin-like growth factor binding protein-3 (IGFBP-3) is emerging as a critical regulator of cell survival. There has been no study which directly examined the potential role for this major growth factor in the programmed cell death (apoptosis) of insulin-secreting cells. To determine whether IGFBP-3 mediates apoptosis in insulin-secreting cells, we performed a rigorous series of experiments with the rat insulinoma (RIN) cell line m5F and the hamster insulin-secreting tumor (HIT) T-15. Within 24 h exogenous IGFBP-3 induced significant DNA fragmentation in RIN and HIT cells, at doses ranging from 4.4 to 2000 ng/ml (P<0.05) without a classic dose-response relationship. DNA fragmentation induced by rhIGFBP-3 occurred in the presence of immunoglobulin to block the type 1 IGF receptor. As detected by flow cytometry for Annexin V exposure to the cell surface, rhIGFBP-3 treatment doubled the proportion of apoptotic HIT cells from 1.7 +/- 0.4% (serum-free control) to 3.4 +/- 0.2% (P<0.02), an effect completely reversed by co-treatment with 1000 ng/ml rhIGF-I. Immunofluorescent microscopy disclosed that pro-inflammatory Th1 cytokines increased intranuclear aggregation of endogenous IGFBP-3. Cytokine-induced DNA fragmentation was completely blocked by relatively brief pre-treatment with antisense IGFBP-3 phosphorothioate oligodeoxynucleotides. In conclusion, we have presented the first evidence that IGFBP-3 contributes to cytokine-mediated apoptosis in insulin-secreting cells.


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CRRD Object Information
CRRD ID: 10402776
Created: 2015-10-28
Species: All species
Last Modified: 2015-10-28
Status: ACTIVE


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