ArticleProceedings of the National Academy of Sciences of the United States of America2022
Alternative splicing encodes functional intracellular CD59 isoforms that mediate insulin secretion and are down-regulated in diabetic islets.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Immune Biomarkers of Islet Transplant Rejection Revealed by Synthetic Immunological Niche.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CD59 drives diet-induced obesity and glucose intolerance, insulin resistance, and metabolic dysfunction-associated steatotic liver disease.npj metabolic health and disease · 2026Article
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- The secret life of complement: challenges and opportunities in exploring functions of the complosome in disease.The Journal of clinical investigation · 2025Review
- The multiverse of CD46 and oncologic interactions.The Journal of clinical investigation · 2025Review
- Neuronal CD59 isoforms IRIS-1 and IRIS-2 as regulators of neurotransmitter release with implications for Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59.International journal of molecular sciences · 2024Article
- Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis.Communications biology · 2024Article
- Emerging role of complement in COVID-19 and other respiratory virus diseases.Cellular and molecular life sciences : CMLS · 2024Review
- A guide to complement biology, pathology and therapeutic opportunity.Nature reviews. Immunology · 2024Review
- The complement system in lipid-mediated pathologies.Frontiers in immunology · 2024Review
- Complement, complosome, and complotype: A perspective.European journal of immunology · 2023Review
- The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.Nature structural & molecular biology · 2023Review
- Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma.International journal of molecular sciences · 2023Review
- Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction.Cell communication and signaling : CCS · 2023Review
- Complosome - the intracellular complement system.Nature reviews. Nephrology · 2023Review
- Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes.Diabetology & metabolic syndrome · 2023Article
- Intracellular complement: Evidence, definitions, controversies, and solutions.Immunological reviews · 2023Review
- The role of the complosome in health and disease.Frontiers in immunology · 2023Review
- CD59-Regulated Ras Compartmentalization Orchestrates Antitumor T-cell Immunity.Cancer immunology research · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pancreatic islets highly express CD59, which is a glycosylphosphatidylinositol (GPI)-anchored cell-surface protein and is required for insulin secretion. How cell-surface CD59 could interact with intracellular exocytotic machinery has so far not been described. We now demonstrate the existence of CD59 splice variants in human pancreatic islets, which have unique C-terminal domains replacing the GPI-anchoring signal sequence. These isoforms are found in the cytosol of β-cells, interact with SNARE proteins VAMP2 and SNAP25, colocalize with insulin granules, and rescue insulin secretion in CD59-knockout (KO) cells. We therefore named these isoforms IRIS-1 and IRIS-2 (Isoforms Rescuing Insulin Secretion 1 and 2). Antibodies raised against each isoform revealed that expression of both IRIS-1 and IRIS-2 is significantly lower in islets isolated from human type 2 diabetes (T2D) patients, as compared to healthy controls. Further, glucotoxicity induced in primary, healthy human islets led to a significant decrease of IRIS-1 expression, suggesting that hyperglycemia (raised glucose levels) and subsequent decreased IRIS-1 expression may contribute to relative insulin deficiency in T2D patients. Similar isoforms were also identified in the mouse CD59B gene, and targeted CRISPR/Cas9-mediated knockout showed that these intracellular isoforms, but not canonical CD59B, are involved in insulin secretion from mouse β-cells. Mouse IRIS-2 is also down-regulated in diabetic db/db mouse islets. These findings establish the endogenous existence of previously undescribed non–GPI-anchored intracellular isoforms of human CD59 and mouse CD59B, which are required for normal insulin secretion.
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.