期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 209, 期 1-2, 页码 17-31出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/j.mce.2003.08.003
关键词
insulin receptor substrate-2 (IRS-2); pancreatic beta-cell; apoptosis; signal transduction; free fatty acid
资金
- NIDDK NIH HHS [DK 55269, DK60266] Funding Source: Medline
IRS-2 plays a pivotal role in the control of pancreatic P-cell growth. Here, the effect of altering IRS-2 expression levels in the pancreatic p-cell line, INS-1, was examined. Adenoviral-mediated increased in IRS-2 protein levels protected against fatty acid (FFA)-induced apoptosis, associated with increased activation of PKB and decreased levels of activated caspase-9. Conversely, decreasing endogenous IRS-2 in INS-1 cells, using adenoviral-mediated expression of IRS-2 antisense, caused a three-fold increase in baseline apoptosis that was further enhanced in the presence of FFA. This was associated with decreased activation of PKB and increased caspase-9 activation. Although IRS-4 is not normally expressed in p-cells, it was found that adenoviral-mediated introduction of IRS-4 into INS-1 cells enhanced glucose/IGF-1 induced mitogenesis, and protected against FFA-induced apoptosis, similarly to IRS-2. Moreover, expression of IRS-4 in INS-1 cells depleted of IRS-2 levels by IRS-2 antisense, was able to compensate for the lack of IRS-2 and reduce apoptosis in these cells back to normal. Thus, in P-cells IRS-4 and -2 have similar biological functions. Also, this study further emphasizes the importance of IRS-2 signaling in control of p-cell survival. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
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