ArticleProceedings of the National Academy of Sciences of the United States of America2015
Apolipoprotein CIII links islet insulin resistance to β-cell failure in diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review.Cardiovascular diabetology · 2022Pooled it
- ApoC-III and ectopic fat accumulation in individuals with type 2 diabetes: an exploratory analysis from the MEDEA randomised controlled study.Diabetologia · 2025Trial
- Volanesorsen, an antisense oligonucleotide to apolipoprotein C-III, increases lipoprotein lipase activity and lowers triglycerides in partial lipodystrophy.Journal of clinical lipidologyTrial
- siRNA-Mediated Reduction of Apolipoprotein CIII Delays Pancreatic Islet Deterioration and Onset of Type 1 Diabetes in Diabetes-Prone BioBreeding Rats.Biomedicines · 2026Article
- Apolipoprotein C-III: Risk-factor, Regulator of Triglyceride-rich Lipoprotein Metabolism and Therapeutic Target.Current atherosclerosis reports · 2026Review
- Discovery of NovelGenes · 2025Article
- ApoC-III proteoforms are associated with better lipid, inflammatory, and glucose profiles independent of total apoC-III.Cardiovascular diabetology · 2024Article
- Multifaceted Role of Apolipoprotein C3 in Cardiovascular Disease Risk and Metabolic Disorder in Diabetes.International journal of molecular sciences · 2024Review
- Review
- Exploring apolipoprotein C-III: pathophysiological and pharmacological relevance.Cardiovascular research · 2024Review
- ApoC3 is expressed in oocytes and increased expression is associated with PCOS progression.Journal of ovarian research · 2023Article
- Quartet of APOCs and the Different Roles They Play in Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Interventional hepatic apoC-III knockdown improves atherosclerotic plaque stability and remodeling by triglyceride lowering.JCI insight · 2022Article
- Is apoCIII-Lowering A Double-Edged Sword?Journal of atherosclerosis and thrombosis · 2022Article
- Apolipoprotein C-III is linked to the insulin resistance and beta-cell dysfunction that are present in rheumatoid arthritis.Arthritis research & therapy · 2022Article
- Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Apolipoprotein CIII Reduction Protects White Adipose Tissues against Obesity-Induced Inflammation and Insulin Resistance in Mice.International journal of molecular sciences · 2021Article
- Guanidinylated Apolipoprotein C3 (ApoC3) Associates with Kidney and Vascular Injury.Journal of the American Society of Nephrology : JASN · 2021Observational
- Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues.International journal of molecular sciences · 2021Review
- Ectopic Leptin Production by Intraocular Pancreatic Islet Organoids Ameliorates the Metabolic Phenotype ofMetabolites · 2021Article
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Insulin resistance and β-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and β-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of β-cell cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca(2+)]i response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of β-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.
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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.