ArticleDiabetes2013
Glucokinase activation ameliorates ER stress-induced apoptosis in pancreatic β-cells.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Balancing efficacy and safety: glucokinase activators in glycemic and metabolic management of type 2 diabetes mellitus-a meta-analysis.Endocrine journal · 2025Pooled it
- Resetting the glucose sensor: dorzagliatin and the evolution of glucokinase activation in diabetes therapy.BMJ open diabetes research & care · 2026Review
- Proteostasis in the regulation of pancreatic islet cell plasticity.Journal of diabetes investigation · 2026Review
- Recent advances in pancreatic β-cell dysfunction in type 2 diabetes mellitus: Intracellular stress and dedifferentiation.Journal of diabetes investigation · 2026Article
- Article
- Imeglimin suppresses glucagon secretion and induces a loss of α cell identity.Cell reports. Medicine · 2025Article
- Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism.Molecular metabolism · 2025Article
- Expression analysis and possible functional roles of semaphorin/plexin/CRMP families in mouse pancreatic islets.Scientific reports · 2025Article
- Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis.Cellular & molecular biology letters · 2024Review
- Uncovering the function of insulin receptor substrate in termites' immunity through active immunization.Journal of insect science (Online) · 2024Article
- Insights to the emerging potential of glucokinase activators as antidiabetic agent.Pharmaceutical patent analyst · 2024Review
- Endoplasmic reticulum stress in pancreatic β-cell dysfunctionality and diabetes mellitus: a promising target for generation of functional hPSC-derived β-cellsFrontiers in endocrinology · 2024Review
- Glucokinase activator improves glucose tolerance and induces hepatic lipid accumulation in mice with diet-induced obesity.Liver research (Beijing, China) · 2023Article
- β-Cell glucokinase expression was increased in type 2 diabetes subjects with better glycemic control.Journal of diabetes · 2023Article
- Protective effects of S100A8 on sepsis mortality: Links to sepsis risk in obesity and diabetes.iScience · 2022Article
- Novel Loss-of-Function Variant in HNF1a Induces β-Cell Dysfunction through Endoplasmic Reticulum Stress.International journal of molecular sciences · 2022Article
- E2F1 transcription factor mediates a link between fat and islets to promote β cell proliferation in response to acute insulin resistance.Cell reports · 2022Article
- XAF1 overexpression exacerbates diabetes by promoting pancreatic β-cell apoptosis.Acta diabetologica · 2022Article
- Article
- Macrophages and neutrophils are necessary for ER stress-induced β cell loss.Cell reports · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The derangement of endoplasmic reticulum (ER) homeostasis triggers β-cell apoptosis, leading to diabetes. Glucokinase upregulates insulin receptor substrate 2 (IRS-2) expression in β-cells, but the role of glucokinase and IRS-2 in ER stress has been unclear. In this study, we investigated the impact of glucokinase activation by glucokinase activator (GKA) on ER stress in β-cells. GKA administration improved β-cell apoptosis in Akita mice, a model of ER stress-mediated diabetes. GKA increased the expression of IRS-2 in β-cells, even under ER stress. Both glucokinase-deficient Akita mice and IRS-2-deficient Akita mice exhibited an increase in β-cell apoptosis, compared with Akita mice. β-cell-specific IRS-2-overexpressing (βIRS-2-Tg) Akita mice showed less β-cell apoptosis than Akita mice. IRS-2-deficient islets were vulnerable, but βIRS-2-Tg islets were resistant to ER stress-induced apoptosis. Meanwhile, GKA regulated the expressions of C/EBP homologous protein (CHOP) and other ER stress-related genes in an IRS-2-independent fashion in islets. GKA suppressed the expressions of CHOP and Bcl2-associated X protein (Bax) and protected against β-cell apoptosis under ER stress in an ERK1/2-dependent, IRS-2-independent manner. Taken together, GKA ameliorated ER stress-mediated apoptosis by harmonizing IRS-2 upregulation and the IRS-2-independent control of apoptosis in β-cells.
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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.