ArticleThe Journal of clinical investigation1993
Chronic exposure of HIT cells to high glucose concentrations paradoxically decreases insulin gene transcription and alters binding of insulin gene regulatory protein.
Article in The Journal of clinical investigation, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.
- Variable phenotypes of individual and family monogenic cases with hyperinsulinism and diabetes: a systematic review.Reviews in endocrine & metabolic disorders · 2022Pooled it
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- Nrf2 and Antioxidant Response in Animal Models of Type 2 Diabetes.International journal of molecular sciences · 2023Review
- New insights into the role of melatonin in diabetic cardiomyopathy.Pharmacology research & perspectives · 2022Review
- Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management.Frontiers in endocrinology · 2022Review
- Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells.Frontiers in endocrinology · 2022Review
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- FoxA2 and RNA Pol II mediate human islet amyloid polypeptide turnover in ER-stressed pancreatic β-cells.The Biochemical journal · 2021Article
- Pharmacological Inhibition of Inositol-Requiring Enzyme 1α RNase Activity Protects Pancreatic Beta Cell and Improves Diabetic Condition in Insulin Mutation-Induced Diabetes.Frontiers in endocrinology · 2021Article
- Glucose transporters in pancreatic islets.Pflugers Archiv : European journal of physiology · 2020Review
- Overexpression of Galectin 3 in Pancreatic β Cells Amplifies β-Cell Apoptosis and Islet Inflammation in Type-2 Diabetes in Mice.Frontiers in endocrinology · 2020Article
- Islet-specific Prmt5 excision leads to reduced insulin expression and glucose intolerance in mice.The Journal of endocrinology · 2020Article
- Lysosomal degradation of newly formed insulin granules contributes to β cell failure in diabetes.Nature communications · 2019Article
- PIAS-family proteins negatively regulate Glis3 transactivation function through SUMO modification in pancreatic β cells.Heliyon · 2018Article
- Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells.Journal of cellular and molecular medicine · 2018Article
- Article
- Nrf2/antioxidant pathway mediates β cell self-repair after damage by high-fat diet-induced oxidative stress.JCI insight · 2017Article
- The ethyl acetate fraction of corn silk exhibits dual antioxidant and anti-glycation activities and protects insulin-secreting cells from glucotoxicity.BMC complementary and alternative medicine · 2016Article
- Discovery, Synthesis, and Evaluation of 2,4-Diaminoquinazolines as a Novel Class of Pancreatic β-Cell-Protective Agents against Endoplasmic Reticulum (ER) Stress.Journal of medicinal chemistry · 2016Article
6 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
Abstract
Chronically culturing HIT-T15 cells in media containing high glucose concentrations leads to decreased insulin mRNA levels, insulin content, and insulin secretion. These changes can be prevented by culturing the cells in media containing lower glucose levels (Robertson, R. P., H.-J. Zhang, K. L. Pyzdrowski, and T. F. Walseth. 1992. J. Clin. Invest. 90:320-325). The mechanism of this seemingly paradoxical phenomenon was examined by transiently transfecting HIT cells with a chloramphenicol acetyl transferase (CAT) reporter gene controlled by the 5'-regulatory domain of the human insulin gene (INSCAT). Early passages of HIT cells readily expressed INSCAT, whereas late passages of cells chronically cultured in 11.1 mM glucose expressed only 28.7 +/- 2.3% (mean +/- SEM) of the CAT activity expressed in early passages. In contrast, late passages of HIT cells chronically cultured in 0.8 mM glucose retained the ability to express the INSCAT reporter gene to 69.6 +/- 10.0% of the CAT activity observed in early passages. The decrease in INSCAT expression in late passages of cells serially cultured in 11.1 mM glucose was associated with the inability to form a specific nuclear protein-DNA complex with the CT motifs of the human insulin promoter. Formation of this specific protein-DNA complex was preserved in late passages of HIT cells when serially cultured in 0.8 mM glucose. Mutations of the CT motifs caused markedly diminished CAT activity in all passages examined. These data indicate that chronic exposure of the beta cell to high glucose concentrations can paradoxically decrease insulin gene transcription, in part, by altering the ability of a regulatory protein (GSTF) to interact with the insulin gene promoter. This provides a potential mechanism for glucotoxic effects on the beta cell at the level of the insulin gene.
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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.