ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
Episodic β-cell death and dedifferentiation during diet-induced obesity and dysglycemia in male mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.Cell reports. Medicine · 2023Trial
- Investigational treatments of β-cell failure and replacement.Diabetology international · 2026Review
- Article
- β-cell dedifferentiation in type 2 diabetes: Interplay of metabolic stress, endoplasmic reticulum dysfunction, and forkhead box protein O1 inhibition.World journal of diabetes · 2025Article
- Endoplasmic reticulum stress and forkhead box protein O1 inhibition mediate palmitic acid and high glucose-induced β-cell dedifferentiation.World journal of diabetes · 2025Article
- 12-Lipoxygenase Inhibition Improves Glycemia and Obesity-associated Inflammation in Male Human Gene Replacement Mice.Endocrinology · 2025Article
- Terazosin, a repurposed GPR119 agonist, ameliorates mitophagy and β-cell function in NAFPD by inhibiting MST1-Foxo3a signalling pathway.Cell proliferation · 2025Article
- Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.The Journal of biological chemistry · 2025Article
- Beta cell dedifferentiation in type 1 diabetes: sacrificing function for survival?Frontiers in endocrinology · 2024Article
- Loss of β-cell identity and dedifferentiation, not an irreversible process?Frontiers in endocrinology · 2024Review
- Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity.Scientific reports · 2022Article
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- 12-Lipoxygenase governs the innate immune pathogenesis of islet inflammation and autoimmune diabetes.JCI insight · 2021Article
- Cell-Free DNA Fragments as Biomarkers of Islet β-Cell Death in Obesity and Type 2 Diabetes.International journal of molecular sciences · 2021Review
- Single-Cell Transcriptional Profiling of Mouse Islets Following Short-Term Obesogenic Dietary Intervention.Metabolites · 2020Article
- VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet-Induced Stress.Diabetes · 2020Article
- Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes.Clinical epigenetics · 2020Article
- Cyb5r3 links FoxO1-dependent mitochondrial dysfunction with β-cell failure.Molecular metabolism · 2020Article
- Recent Insights Into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.Science signaling · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Loss of functional islet β-cell mass through cellular death or dedifferentiation is thought to lead to dysglycemia during the progression from obesity to type 2 diabetes. To assess these processes in a mouse model of obesity, we performed measures of circulating cell-free differentially methylated insulin II ( Ins2) DNA as a biomarker of β-cell death and aldehyde dehydrogenase 1 family member A3 (ALDH1A3) and forkhead box 01 (Foxo1) immunostaining as markers of β-cell dedifferentiation. Eight-week-old, C57BL/6J mice were fed a low-fat diet (LFD; 10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) and were followed longitudinally for up to 13 wk to measure glycemic control and β-cell mass, death, and dedifferentiation. Compared with LFD controls, β-cell mass increased during the feeding period in HFD animals, and statistically greater β-cell death (unmethylated Ins2) was detectable at 2 and 6 wk after diet initiation. Those times correspond to periods when significant step increases in fasting glucose and glucose intolerance, respectively, were detected. ALDH1A3 and Foxo1 immunostaining of the pancreas revealed evidence of β-cell dedifferentiation by 13 wk when fed an HFD, but not in LFD controls. In conclusion, early episodic β-cell death may be a feature of cellular turnover correlated with changes in glycemia during β-cell mass accrual in obesity, whereas β-cell dedifferentiation may be a feature seen later in established disease.-Tersey, S. A., Levasseur, E. M., Syed, F., Farb, T. B., Orr, K. S., Nelson, J. B., Shaw, J. L., Bokvist, K., Mather, K. J., Mirmira, R. G. Episodic β-cell death and dedifferentiation during diet-induced obesity and dysglycemia in male mice.
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