ArticleDiabetes2005
Chronic hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of beta-cell differentiation and secretory function in the db/db mouse model of diabetes.
Article in Diabetes, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 143 citations in OpenAlex.
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- Intermittent fasting protects β-cell identity and function in a type-2 diabetes model.Metabolism: clinical and experimental · 2024Article
- The glucocorticoid receptor as a master regulator of the Müller cell response to diabetic conditions in mice.Journal of neuroinflammation · 2024Article
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding.Cell death & disease · 2023Article
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- Role of Reactive Oxygen Species in Glucose Metabolism Disorder in Diabetic Pancreatic β-Cells.Biomolecules · 2022Review
- Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure.Nature communications · 2022Article
- XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and protects against diabetic beta cell failure during metabolic stress in mice.Diabetologia · 2022Article
- Effects of Sodium-Glucose Co-Transporter-2 Inhibitors on Pancreatic β-Cell Mass and Function.International journal of molecular sciences · 2022Review
- Recent Advances in Understanding Nrf2 Agonism and Its Potential Clinical Application to Metabolic and Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion.International journal of molecular sciences · 2021Review
- The Plasticity of Pancreatic β-Cells.Metabolites · 2021Review
- Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and Above Metal Homeostasis and Antioxidant Response.Biology · 2021Review
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- RETRACTED: Molecular targeting of FATP4 transporter for oral delivery of therapeutic peptide.Science advances · 2020Article
- Inadequate β-cell mass is essential for the pathogenesis of type 2 diabetes.The lancet. Diabetes & endocrinology · 2020Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The beta-cell is a highly specialized cell with a unique differentiation that optimizes glucose-induced insulin secretion (GIIS). Here, we evaluated changes in gene expression that accompany beta-cell dysfunction in the db/db mouse model of type 2 diabetes. In db/db islets, mRNA levels of many genes implicated in beta-cell glucose sensing were progressively reduced with time, as were several transcription factors important for the maintenance of beta-cell differentiation. Conversely, genes normally suppressed in beta-cells, such as a variety of stress response mediators and inhibitor of differentiation/DNA binding 1, a gene capable of inhibiting differentiation, were markedly increased. We assessed whether this global alteration in the pattern of beta-cell gene expression was related more to chronic hyperglycemia or hyperlipidemia; db/db mice were treated with phlorizin, which selectively lowered plasma glucose, or bezafibrate, which selectively lowered plasma lipids. GIIS as well as the majority of the changes in gene expression were completely normalized by lowering glucose but were unaffected by lowering lipids. However, the restoration of GIIS was not accompanied by normalized uncoupling protein 2 or peroxisome proliferator-activated receptor gamma mRNA levels, which were upregulated in db/db islets. These studies demonstrate that hyperglycemia, independent of plasma lipid levels, is sufficient for the loss of beta-cell differentiation and secretory function in db/db mice.
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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.