ArticleDiabetologia2022
XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and protects against diabetic beta cell failure during metabolic stress in mice.
Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Targeting the IRE1α/XBP1 pathway in type 2 diabetes mellitus: from ER stress signaling to therapeutic opportunity.Molecular biology reports · 2026Review
- Adipocyte-derived exosomal ANGPTL2 promotes beta cell dysfunction via the EIF2α/ATF4/CHOP stress pathway in mice.Diabetologia · 2026Article
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 2026Article
- Role and mechanism of palmitic acid-regulated palmitoylation modification of SEC63 protein during endoplasmic reticulum stress in human ovarian granulosa tumor cells (KGN).Journal of ovarian research · 2026Article
- Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Review
- Single-cell perturbations decipher ribosomal stress-surveillance regulators in type 2 diabetes.Nature metabolism · 2026Article
- Article
- SwitchTFI: identifying transcription factors driving cell differentiation.Genome biology · 2025Article
- Defining the role of β-cell IRE1α/XBP1 pathway and its gene regulatory network components in non-obese diabetic mice.Nature communications · 2025Article
- Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice.The Journal of clinical investigation · 2025Article
- Article
- Prolonged glucagon exposure rewires lipid oxidation and drives diabetic kidney disease progression.Nature communications · 2025Article
- XBP1 expression in pancreatic islet cells is associated with poor glycaemic control especially in young non-obese onset diabetes across ancestries.Communications medicine · 2025Article
- Unique and conserved endoplasmic reticulum stress responses in neuroendocrine cells.bioRxiv : the preprint server for biology · 2025Article
- Imeglimin suppresses glucagon secretion and induces a loss of α cell identity.Cell reports. Medicine · 2025Article
- Emerging Insights into Brown Adipose Tissue Crosstalk With Pancreatic β-Cells in Metabolic Regulation.Endocrinology · 2025Review
- Berberine treatment inhibits ferroptosis in NIT-1 murine pancreatic cell line via inhibiting OGT expression levels.Scientific reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPancreatic beta cell dedifferentiation, transdifferentiation into other islet cells and apoptosis have been implicated in beta cell failure in type 2 diabetes, although the mechanisms are poorly defined. The endoplasmic reticulum stress response factor X-box binding protein 1 (XBP1) is a major regulator of the unfolded protein response. XBP1 expression is reduced in islets of people with type 2 diabetes, but its role in adult differentiated beta cells is unclear. Here, we assessed the effects of Xbp1 deletion in adult beta cells and tested whether XBP1-mediated unfolded protein response makes a necessary contribution to beta cell compensation in insulin resistance states.
methodsMice with inducible beta cell-specific Xbp1 deletion were studied under normal (chow diet) or metabolic stress (high-fat diet or obesity) conditions. Glucose tolerance, insulin secretion, islet gene expression, alpha cell mass, beta cell mass and apoptosis were assessed. Lineage tracing was used to determine beta cell fate.
resultsDeletion of Xbp1 in adult mouse beta cells led to beta cell dedifferentiation, beta-to-alpha cell transdifferentiation and increased alpha cell mass. Cell lineage-specific analyses revealed that Xbp1 deletion deactivated beta cell identity genes (insulin, Pdx1, Nkx6.1, Beta2, Foxo1) and derepressed beta cell dedifferentiation (Aldh1a3) and alpha cell (glucagon, Arx, Irx2) genes. Xbp1 deletion in beta cells of obese ob/ob or high-fat diet-fed mice triggered diabetes and worsened glucose intolerance by disrupting insulin secretory capacity. Furthermore, Xbp1 deletion increased beta cell apoptosis under metabolic stress conditions by attenuating the antioxidant response. CONCLUSIONS/
interpretationThese findings indicate that XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and is required for beta cell compensation and prevention of diabetes in insulin resistance states.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.