J Biol Chem 2022 Jul 18:102283. Epub 2022 Jul 18.
Departments of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Departments of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address:
Knockout of the transcription factor X-box binding protein (XBP1) is known to decrease liver glucose production and lipogenesis. However, whether insulin can regulate gluconeogenesis and lipogenesis through XBP1 and how insulin activates the inositol-requiring enzyme (IRE1)-XBP1 ER stress pathway remain unexplored. Here we report that in the fed state, insulin-activated kinase AKT directly phosphorylates IRE1 at S724, which in turn mediates the splicing of XBP1u mRNA, thus favoring the generation of the spliced form, XBP1s, in the liver of mice. Read More