ArticleExperimental & molecular medicine2018
The IRE1α-XBP1s pathway promotes insulin-stimulated glucose uptake in adipocytes by increasing PPARγ activity.
Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Hepatokines and polycystic ovary syndrome: investigating the connection between the hepato-ovarian axis and disorders in glycolipid metabolism in PCOS: a narrative review.Frontiers in endocrinology · 2026Review
- MIST1 regulates endoplasmic reticulum stress-induced hepatic apoptosis as a candidate marker of fatty liver disease progression.Cell death & disease · 2024Article
- Unveiling Novel Mechanism of CIDEB in Fatty Acid Synthesis Through ChIP-Seq and Functional Analysis in Dairy Goat.International journal of molecular sciences · 2024Article
- Long-chain fatty acids - The turning point between 'mild' and 'severe' acute pancreatitis.Heliyon · 2024Review
- Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.The Journal of biological chemistry · 2024Article
- Experimental periodontitis induced hypoadiponectinemia by IRE1α-mediated endoplasmic reticulum stress in adipocytes.BMC oral health · 2023Article
- Review
- X-box Binding Protein 1: An Adaptor in the Pathogenesis of Atherosclerosis.Aging and disease · 2023Review
- Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology.International journal of molecular sciences · 2022Review
- Article
- Adipocyte CAMK2 deficiency improves obesity-associated glucose intolerance.Molecular metabolism · 2021Article
- Roles of XBP1s in Transcriptional Regulation of Target Genes.Biomedicines · 2021Review
- Advances in Biological Functions and Clinical Studies of FGF21.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The peroxisome proliferator-activated receptor-γ (PPARγ) improves whole-body insulin sensitivity by regulating the adipogenic and metabolic functions of mature adipocytes. We have previously demonstrated that an active splice variant of X-box binding protein 1 (XBP1s) enhances PPARγ expression during adipogenesis. In this study, we investigated the role of XBP1s, particularly with respect to PPARγ, in the mechanisms underlying insulin sensitivity in mature adipocytes. Insulin was able to stimulate XBP1s generation by activating inositol-requiring enzyme 1 (IRE1) α and was also able to increase its transcriptional activity by inducing nuclear translocation. XBP1s also upregulated the levels of phosphorylated IRS1 and AKT, demonstrating a positive feedback regulatory mechanism linking insulin and XBP1s. XBP1s enhanced the expression of fibroblast growth factor 21 and, in turn, increased PPARγ activity, translocation of GLUT4 to the cell surface, and glucose uptake rate in adipocytes. In addition, XBP1s abolished palmitate-induced insulin resistance in adipocytes by increasing adiponectin secretion, repressing the secretion of pro-inflammatory adipokines such as leptin, monocyte chemoattractant protein 1, and tumor necrosis factor α, and decreasing fatty acid release. These findings provide a novel mechanism by which XBP1s stimulate insulin sensitivity in adipocytes through fibroblast growth factor 21 induction and PPARγ activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.