ArticlePloS one2011
Glucose and fatty acids synergize to promote B-cell apoptosis through activation of glycogen synthase kinase 3β independent of JNK activation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Antioxidant and Antidiabetic Properties of a Thinned-Nectarine-Based Nanoformulation in a Pancreatic β-Cell Line.Antioxidants (Basel, Switzerland) · 2023Article
- Gsk-3-Mediated Proteasomal Degradation of ATF4 Is a Proapoptotic Mechanism in Mouse Pancreatic β-Cells.International journal of molecular sciences · 2022Article
- The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus.European thyroid journal · 2022Article
- Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes?International journal of molecular sciences · 2021Review
- Beta Cell Physiological Dynamics and Dysfunctional Transitions in Response to Islet Inflammation in Obesity and Diabetes.Metabolites · 2020Review
- Bax and Bak jointly control survival and dampen the early unfolded protein response in pancreatic β-cells under glucolipotoxic stress.Scientific reports · 2020Article
- Upregulation of lipid metabolism genes in the breast prior to cancer diagnosis.NPJ breast cancer · 2020Article
- A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor.Environmental science and pollution research international · 2018Article
- Interorgan Crosstalk Contributing toJournal of diabetes research · 2017Review
- RNA-binding protein HuD reduces triglyceride production in pancreatic β cells by enhancing the expression of insulin-induced gene 1.Biochimica et biophysica acta · 2016Article
- A20 Inhibits β-Cell Apoptosis by Multiple Mechanisms and Predicts Residual β-Cell Function in Type 1 Diabetes.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity.Journal of diabetes research · 2016Article
- Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis.Oncotarget · 2015Article
- Therapeutic Approaches for Preserving or Restoring Pancreatic β-Cell Function and Mass.Diabetes & metabolism journal · 2014Review
- Atorvastatin helps preserve pancreatic β cell function in obese C57BL/6 J mice and the effect is related to increased pancreas proliferation and amelioration of endoplasmic-reticulum stress.Lipids in health and disease · 2014Article
- Valproate pretreatment protects pancreatic β-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3β.Journal of biomedical science · 2014Article
- Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity.BMC cell biology · 2013Article
- Article
- Endoplasmic reticulum stress and type 2 diabetes.Annual review of biochemistry · 2012Review
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe combination of elevated glucose and free-fatty acids (FFA), prevalent in diabetes, has been suggested to be a major contributor to pancreatic β-cell death. This study examines the synergistic effects of glucose and FFA on β-cell apoptosis and the molecular mechanisms involved. Mouse insulinoma cells and primary islets were treated with palmitate at increasing glucose and effects on apoptosis, endoplasmic reticulum (ER) stress and insulin receptor substrate (IRS) signaling were examined. PRINCIPAL
findingsIncreasing glucose (5-25 mM) with palmitate (400 µM) had synergistic effects on apoptosis. Jun NH2-terminal kinase (JNK) activation peaked at the lowest glucose concentration, in contrast to a progressive reduction in IRS2 protein and impairment of insulin receptor substrate signaling. A synergistic effect was observed on activation of ER stress markers, along with recruitment of SREBP1 to the nucleus. These findings were confirmed in primary islets. The above effects associated with an increase in glycogen synthase kinase 3β (Gsk3β) activity and were reversed along with apoptosis by an adenovirus expressing a kinase dead Gsk3β. CONCLUSIONS/SIGNIFICANCE: Glucose in the presence of FFA results in synergistic effects on ER stress, impaired insulin receptor substrate signaling and Gsk3β activation. The data support the importance of controlling both hyperglycemia and hyperlipidemia in the management of Type 2 diabetes, and identify pancreatic islet β-cell Gsk3β as a potential therapeutic target.
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