[HTML][HTML] Insulin receptor substrate-2 proteasomal degradation mediated by a mammalian target of rapamycin (mTOR)-induced negative feedback down-regulates …

I Briaud, LM Dickson, MK Lingohr, JF McCuaig… - Journal of Biological …, 2005 - ASBMB
Regulation of insulin receptor substrate (IRS)-2 expression is critical to β-cell survival, but
the mechanisms that control this are complex and undefined. Here in pancreatic β-cells (INS-
1), chronic exposure (> 8 h) to 15 mm glucose and/or 5 nm IGF-1, increased Ser/Thr
phosphorylation of IRS-2, which correlated with decreased IRS-2 levels. This glucose/IGF-1-
induced decrease in IRS-2 levels was prevented by the proteasomal inhibitor, lactacystin. In
addition, the glucose/IGF-1-induced increase in Ser/Thr phosphorylation of IRS-2 and the …