ArticleNature metabolism2021
Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Exploring Biomarkers in Type 2 Diabetes Mellitus versus Normoglycemia Identified through High-Throughput Proteomics: A Systematic Review and Meta-Analysis.Journal of proteome research · 2026Pooled it
- Spatially resolved lipid compartmentalization in human pancreatic islets revealed by high-resolution ultra-low-flow-rate desorption electrospray ionization mass spectrometry imaging.Analytical and bioanalytical chemistry · 2026Article
- Proteomic analysis of pancreatic endocrine cells by mechanistic single-cell isolation identifies membrane pathways.Experimental & molecular medicine · 2026Article
- Islet ultrastructure: past achievements and future directions.Diabetologia · 2026Review
- Histopathological and Transcriptomic Alterations in Metabolic Organs: A Case Study from a Spontaneously Diabetic Rhesus Macaque.International journal of molecular sciences · 2026Article
- Article
- Temporal single-cell transcriptional dynamics of murine pancreatic islet remodeling during hyperglycaemia progression.Molecular metabolism · 2026Article
- Review
- Integrative multi-omics analysis unravels the metabolic landscape and reveals serum biomarkers for early diagnosis of hyperuricemia.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- From pancreas and islet resources to diabetes insights.Diabetologia · 2026Review
- Identification of Biomarkers forCurrent issues in molecular biology · 2026Article
- Proteomic Analysis on Human Islets Suggests Nucleocytoplasmic Transport as a Mechanism of PERK Attenuation Effects in Diabetes.Molecular & cellular proteomics : MCP · 2026Article
- Polyadenylation of insulin mRNA by Tent5a regulates pancreatic beta cells.Nature communications · 2026Article
- Heterogeneous endocrine cell composition defines human islet functional phenotypes.Nature communications · 2026Article
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 2026Article
- Impaired glucose tolerance and mild diabetes induce β-cell dysfunction in mice.Nature communications · 2026Article
- Contrasting Effects of Chronic Glucokinase Activation and Inhibition on Pancreatic Beta-Cell Function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Glycine-GLRA1-calmodulin signaling regulates endoplasmic reticulum calcium to sustain insulin secretion and β-cell function.Life metabolism · 2026Article
- Article
- BPX-Net: biomarker-preserved explainable networks for disease diagnosis and prognosis.BioData mining · 2026Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most research on human pancreatic islets is conducted on samples obtained from normoglycaemic or diseased brain-dead donors and thus cannot accurately describe the molecular changes of pancreatic islet beta cells as they progress towards a state of deficient insulin secretion in type 2 diabetes (T2D). Here, we conduct a comprehensive multi-omics analysis of pancreatic islets obtained from metabolically profiled pancreatectomized living human donors stratified along the glycemic continuum, from normoglycemia to T2D. We find that islet pools isolated from surgical samples by laser-capture microdissection display remarkably more heterogeneous transcriptomic and proteomic profiles in patients with diabetes than in non-diabetic controls. The differential regulation of islet gene expression is already observed in prediabetic individuals with impaired glucose tolerance. Our findings demonstrate a progressive, but disharmonic, remodelling of mature beta cells, challenging current hypotheses of linear trajectories toward precursor or transdifferentiation stages in T2D. Furthermore, through integration of islet transcriptomics with preoperative blood plasma lipidomics, we define the relative importance of gene coexpression modules and lipids that are positively or negatively associated with HbA1c levels, pointing to potential prognostic markers.
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