ArticleThe Journal of biological chemistry2013
Hyperplasia of pancreatic beta cells and improved glucose tolerance in mice deficient in the FXYD2 subunit of Na,K-ATPase.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Generation of human islet cell type-specific identity genesets.Nature communications · 2022Pooled it
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- The functions of FXYD family members in human health and disease.Genes & diseases · 2026Review
- Knockdown of FXYD2 inhibits mepivacaine-induced cardiomyocyte injury by activating the PI3K/AKT signaling pathway.European journal of medical research · 2025Article
- FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction.Nature communications · 2025Article
- Kinesin-1 mediates proper ER folding of the CaEMBO reports · 2024Article
- scParser: sparse representation learning for scalable single-cell RNA sequencing data analysis.Genome biology · 2024Article
- Inferring regulators of cell identity in the human adult pancreas.NAR genomics and bioinformatics · 2023Article
- Single-nucleus RNA-Seq reveals singular gene signatures of human ductal cells during adaptation to insulin resistance.JCI insight · 2022Article
- Lessons from single-cell RNA sequencing of human islets.Diabetologia · 2022Review
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- Mechanisms controlling pancreatic islet cell function in insulin secretion.Nature reviews. Molecular cell biology · 2021Review
- Beta Cell Imaging-From Pre-Clinical Validation to First in Man Testing.International journal of molecular sciences · 2020Review
- Identification of core genes and pathways in type 2 diabetes mellitus by bioinformatics analysis.Molecular medicine reports · 2019Article
- Chronic Adrenergic Signaling Causes Abnormal RNA Expression of Proliferative Genes in Fetal Sheep Islets.Endocrinology · 2018Article
- Valproic Acid Exposure of Pregnant Rats During Organogenesis Disturbs Pancreas Development in Insulin Synthesis and Secretion of the Offspring.Toxicological research · 2018Article
- Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis.Molecular metabolism · 2017Review
- Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue.The Journal of clinical investigation · 2017Article
- The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease.Frontiers in physiology · 2017Review
- Evidence for Loss in Identity, De-Differentiation, andFrontiers in genetics · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Restoration of the functional potency of pancreatic islets either through enhanced proliferation (hyperplasia) or increase in size (hypertrophy) of beta cells is a major objective for intervention in diabetes. We have obtained experimental evidence that global knock-out of a small, single-span regulatory subunit of Na,K-ATPase, FXYD2, alters glucose control. Adult Fxyd2(-/-) mice showed significantly lower blood glucose levels, no signs of peripheral insulin resistance, and improved glucose tolerance compared with their littermate controls. Strikingly, there was a substantial hyperplasia in pancreatic beta cells from the Fxyd2(-/-) mice compared with the wild type littermates, compatible with an observed increase in the level of circulating insulin. No changes were seen in the exocrine compartment of the pancreas, and the mice had only a mild, well-adapted renal phenotype. Morphometric analysis revealed an increase in beta cell mass in KO compared with WT mice. This appears to explain a phenotype of hyperinsulinemia. By RT-PCR, Western blot, and immunocytochemistry we showed the FXYD2b splice variant in pancreatic beta cells from wild type mice. Phosphorylation of Akt kinase was significantly higher under basal conditions in freshly isolated islets from Fxyd2(-/-) mice compared with their WT littermates. Inducible expression of FXYD2 in INS 832/13 cells produced a reduction in the phosphorylation level of Akt, and phosphorylation was restored in parallel with degradation of FXYD2. Thus we suggest that in pancreatic beta cells FXYD2 plays a role in Akt signaling pathways associated with cell growth and proliferation.
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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 OpenQuestion graph.