Abstract

X-box binding protein1 (XBP1) especially exerts its fundamental effects in the cellular organelle endoplasmic reticulum (ER) via affecting three trans-membrane stress sensor proteins: PKRlike ER kinase (PERK), inositol-requiring enzyme 1(IRE1) and activating transcription factor 6(ATF6). At the center of XBP1’s broad effects is its remarkable metabolic housekeeper function. XBP1 decreased glucose dysfunction via funneling its effects on improving insulin sensitivity and stimulating insulin secretion. However, XBP1 also yields its double-edged effects, driving the transformation from excess glucose to lipid, which is a key contribution to obesity and T2DM. In this review, we highlight the vital mechanism of XBP1 in manipulating glucose and lipid metabolism involved by multiple signaling pathways.

Keywords: Metabolic regulator/housekeeper, XBP1, PI3K, ER stress, IRE1α, insulin.