Furthermore, metformin also exhibits protective effects on rat insulinoma cells through the suppression of palmitate-induced phosphorylation of eukaryotic initiation factor 2 α (eIF2α), JNK, and insulin receptor substrate-1 (IRS-1) suggesting that the β-cell protective effects of metformin in lipotoxicity may be associated with the suppression of ER stress [46]. Here, IRS1 is linked to pancreatic insulinoma.