ArticleNature metabolism2020
Targeted pharmacological therapy restores β-cell function for diabetes remission.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 144 citations in OpenAlex.
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Activation of GScience advances · 2026Article
- An epigenetic switch in β-cells links mitochondrial stress to inflammatory fate via HMGB1 acetylation.Cell death and differentiation · 2026Article
- Temporal single-cell transcriptional dynamics of murine pancreatic islet remodeling during hyperglycaemia progression.Molecular metabolism · 2026Article
- GLP1-E2 therapy delays autoimmune diabetes in late-stage prediabetic NOD mice and potentiates low-dose anti-CD3 therapy for enhanced disease protection.Diabetologia · 2026Article
- Distinct macrophage and T cell programs shape pancreatic inflammation during metabolic stress and aging.bioRxiv : the preprint server for biology · 2026Article
- Workload-induced changes to cell state contribute to β-cell failure in diabetes.bioRxiv : the preprint server for biology · 2026Article
- LDHA induces beta cell dedifferentiation in diabetes through metabolic and epigenetic reprogramming.Diabetologia · 2026Article
- Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.Nature communications · 2026Article
- Cyclic-imide derivative (5e) attenuates hyperglycemia in type 1 diabetic rats by protecting pancreatic cells and enhancing insulin secretion.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
- The protein deacetylase SIRT2 exerts metabolic control over adaptive β cell proliferation.The Journal of clinical investigation · 2025Article
- Mechanistic insights and approaches for beta cell regeneration.Nature chemical biology · 2025Review
- The Beneficial Impact of a Novel Pancreatic Polypeptide Analogue on Islet Cell Lineage.International journal of molecular sciences · 2025Article
- Dual and Triple Gut Peptide Agonists on the Horizon for the Treatment of Type 2 Diabetes and Obesity. An Overview of Preclinical and Clinical Data.Current obesity reports · 2025Review
- Review
- The role of estrogen in the sex difference for the risk factors of heart failure with preserved ejection fraction.Biology direct · 2025Review
- Single-cell RNA transcriptome uncovers distinct developmental trajectories in the embryonic skeletal muscle of Daheng broiler and Tibetan chicken.BMC genomics · 2025Article
- Single-cell RNA sequencing in studies of type 1 diabetes mellitus: modern state-of-the-art and technical peculiarities.Frontiers in endocrinology · 2025Review
- Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models.Diabetologia · 2025Article
- Recent progress of remission in type 2 diabetes.Therapeutic advances in endocrinology and metabolism · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
27 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dedifferentiation of insulin-secreting β cells in the islets of Langerhans has been proposed to be a major mechanism of β-cell dysfunction. Whether dedifferentiated β cells can be targeted by pharmacological intervention for diabetes remission, and ways in which this could be accomplished, are unknown as yet. Here we report the use of streptozotocin-induced diabetes to study β-cell dedifferentiation in mice. Single-cell RNA sequencing (scRNA-seq) of islets identified markers and pathways associated with β-cell dedifferentiation and dysfunction. Single and combinatorial pharmacology further show that insulin treatment triggers insulin receptor pathway activation in β cells and restores maturation and function for diabetes remission. Additional β-cell selective delivery of oestrogen by Glucagon-like peptide-1 (GLP-1-oestrogen conjugate) decreases daily insulin requirements by 60%, triggers oestrogen-specific activation of the endoplasmic-reticulum-associated protein degradation system, and further increases β-cell survival and regeneration. GLP-1-oestrogen also protects human β cells against cytokine-induced dysfunction. This study not only describes mechanisms of β-cell dedifferentiation and regeneration, but also reveals pharmacological entry points to target dedifferentiated β cells for diabetes remission.
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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.