Figure 1.

X-box-binding protein-1, an endoplasmic reticulum stress transcription factor, plays an essential role in maintaining plasma glucose concentration and glucose tolerance. Indeed, in the liver samples from the fructose-fed rats used in the study, there was a marked increase in the spliced form of X-box-binding protein (XBP)-1 mRNA and nuclear protein, in accordance with the increased activity of mammalian target of rapamycin (mTOR) activity and mitogen-activated protein kinase (p38-MAPK). Thus, although the decreased expression of insulin receptor substrate-2 in liver represents an impairment of insulin signaling, the increased expression and activity of XBP-1 could compensate for this deficit and maintain appropriate gluconeogenesis. PEPCK G6Pc: Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase; FoxO1: Forkhead box protein O1.