ArticleCell death & disease2020
Protection from β-cell apoptosis by inhibition of TGF-β/Smad3 signaling.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Tropomyosin-1 positively regulates TGF-β/Smad3 signaling through STUB1 in arecoline-induced oral submucosal fibrosis.Odontology · 2026Article
- Mitochondrial dysfunction-driven inflammation and β-Cell apoptosis in type 2 diabetes mellitus: mechanistic insights and therapeutic implications.Molecular biology reports · 2026Review
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Activated Human Pancreatic Stellate Cells SignatureCommunication in Type 1 Diabetes.Research square · 2026Article
- Lactobacillus rhamnosus GG Supernatant Improves GLP-1 Secretion Through Attenuating L Cell Lipotoxicity and Modulating Gut Microbiota in Obesity.Probiotics and antimicrobial proteins · 2026Article
- Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- The complex interplay between diabetes mellitus and pancreatic carcinogenesis: deciphering multifactorial mechanisms and identifying emerging therapeutic vulnerabilities.Cell & bioscience · 2025Review
- March5-mediated Trim28 degradation preserves islet β-cell function in mice.Nature communications · 2025Article
- Tongmai Hypoglycemic Capsule Attenuates Myocardial Oxidative Stress and Fibrosis in the Development of Diabetic Cardiomyopathy in Rats.Chinese journal of integrative medicine · 2025Article
- Extracellular matrix proteins refine microenvironments for pancreatic organogenesis from induced pluripotent stem cell differentiation.Theranostics · 2025Article
- Complement C3 promotes islet β-cell dedifferentiation by activating Wnt/β-catenin pathway.iScience · 2024Article
- Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors.Toxicological research · 2024Article
- Multi-Omics Analysis Reveals the Toxicity of Polyvinyl Chloride Microplastics toward BEAS-2B Cells.Toxics · 2024Article
- Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression.International journal of molecular sciences · 2024Review
- Synergism of calycosin and bone marrow-derived mesenchymal stem cells to combat podocyte apoptosis to alleviate adriamycin-induced focal segmental glomerulosclerosis.World journal of stem cells · 2023Article
- Review
- The Canine Pancreatic Extracellular Matrix in Diabetes Mellitus and Pancreatitis: Its Essential Role and Therapeutic Perspective.Animals : an open access journal from MDPI · 2023Review
- Palmitoylation couples insulin hypersecretion with β cell failure in diabetes.Cell metabolism · 2023Article
- Zuogui Jiangtang Shuxin formula Ameliorates diabetic cardiomyopathy miceFrontiers in endocrinology · 2023Article
- Regeneration of Pancreatic β-Cells for Diabetes Therapeutics by Natural DYRK1A Inhibitors.Metabolites · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Prevailing insulin resistance and the resultant hyperglycemia elicits a compensatory response from pancreatic islet beta cells (β-cells) that involves increases in β-cell function and β-cell mass. However, the sustained metabolic stress eventually leads to β-cell failure characterized by severe β-cell dysfunction and progressive loss of β-cell mass. Whereas, β-cell dysfunction is relatively well understood at the mechanistic level, the avenues leading to loss of β-cell mass are less clear with reduced proliferation, dedifferentiation, and apoptosis all potential mechanisms. Butler and colleagues documented increased β-cell apoptosis in pancreas from lean and obese human Type 2 diabetes (T2D) subjects, with no changes in rates of β-cell replication or neogenesis, strongly suggesting a role for apoptosis in β-cell failure. Here, we describe a permissive role for TGF-β/Smad3 in β-cell apoptosis. Human islets undergoing β-cell apoptosis release increased levels of TGF-β1 ligand and phosphorylation levels of TGF-β's chief transcription factor, Smad3, are increased in human T2D islets suggestive of an autocrine role for TGF-β/Smad3 signaling in β-cell apoptosis. Smad3 phosphorylation is similarly increased in diabetic mouse islets undergoing β-cell apoptosis. In mice, β-cell-specific activation of Smad3 promotes apoptosis and loss of β-cell mass in association with β-cell dysfunction, glucose intolerance, and diabetes. In contrast, inactive Smad3 protects from apoptosis and preserves β-cell mass while improving β-cell function and glucose tolerance. At the molecular level, Smad3 associates with Foxo1 to propagate TGF-β-dependent β-cell apoptosis. Indeed, genetic or pharmacologic inhibition of TGF-β/Smad3 signals or knocking down Foxo1 protects from β-cell apoptosis. These findings reveal the importance of TGF-β/Smad3 in promoting β-cell apoptosis and demonstrate the therapeutic potential of TGF-β/Smad3 antagonism to restore β-cell mass lost in diabetes.
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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.