ArticlePloS one2016
Resolving Discrepant Findings on ANGPTL8 in β-Cell Proliferation: A Collaborative Approach to Resolving the Betatrophin Controversy.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Contribution of Liver and Pancreatic Islet Crosstalk to β-Cell Function/Dysfunction in the Presence of Fatty Liver.Frontiers in endocrinology · 2022Pooled it
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- Pump-Less, Recirculating Organ-on-Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver.Advanced healthcare materials · 2024Article
- Circulating ANGPTL8 as a Potential Protector of Metabolic Complications in Patients with Psoriasis.Journal of clinical medicine · 2023Article
- Analysis of a genetic region affecting mouse body weight.Physiological genomics · 2023Article
- Islet Biology During COVID-19: Progress and Perspectives.Canadian journal of diabetes · 2022Review
- Newly discovered endocrine functions of the liver.World journal of hepatology · 2021Review
- Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome.Journal of endocrinological investigation · 2021Article
- Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans.Scientific reports · 2021Article
- ANGPTL8 roles in proliferation, metabolic diseases, hypothyroidism, polycystic ovary syndrome, and signaling pathways.Molecular biology reports · 2021Review
- Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era.Journal of translational medicine · 2021Review
- Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus.Frontiers in endocrinology · 2021Article
- Generation and Characterization of a Novel Mouse Model That Allows Spatiotemporal Quantification of Pancreatic β-Cell Proliferation.Diabetes · 2020Article
- Deciphering the expression dynamics of ANGPTL8 associated regulatory network in insulin resistance using formal modelling approaches.IET systems biology · 2020Article
- Evidences for Expression and Location of ANGPTL8 in Human Adipose Tissue.Journal of clinical medicine · 2020Article
- Angiopoietin-like 8 (ANGPTL8) expression is regulated by miR-143-3p in human hepatocytes.Gene · 2019Article
- Chimeric antigen receptor (CAR) T cells targeting a pathogenic MHC class II:peptide complex modulate the progression of autoimmune diabetes.Journal of autoimmunity · 2019Article
- CD19+IgM+ cells demonstrate enhanced therapeutic efficacy in type 1 diabetes mellitus.JCI insight · 2018Article
- (Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives.Physiological reviews · 2018Review
- Impaired β-cell glucokinase as an underlying mechanism in diet-induced diabetes.Disease models & mechanisms · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The β-cell mitogenic effects of ANGPTL8 have been subjected to substantial debate. The original findings suggested that ANGPTL8 overexpression in mice induced a 17-fold increase in β-cell proliferation. Subsequent studies in mice contested this claim, but a more recent report in rats supported the original observations. These conflicting results might be explained by variable ANGPTL8 expression and differing methods of β-cell quantification. To resolve the controversy, three independent labs collaborated on a blinded study to test the effects of ANGPTL8 upon β-cell proliferation. Recombinant human betatrophin (hBT) fused to maltose binding protein (MBP) was delivered to mice by intravenous injection. The results demonstrate that ANGPTL8 does not stimulate significant β-cell proliferation. Each lab employed different methods for β-cell identification, resulting in variable quantification of β-cell proliferation and suggests a need for standardizing practices for β-cell quantification. We also observed a new action of ANGPTL8 in stimulating CD45+ hematopoietic-derived cell proliferation which may explain, in part, published discrepancies. Overall, the hypothesis that ANGPTL8 induces dramatic and specific β-cell proliferation can no longer be supported. However, while ANGPTL8 does not stimulate robust β-cell proliferation, the original experimental model using drug-induced (S961) insulin resistance was validated in subsequent studies, and thus still represents a robust system for studying signals that are either necessary or sufficient for β-cell expansion. As an added note, we would like to commend collaborative group efforts, with repetition of results and procedures in multiple laboratories, as an effective method to resolve discrepancies in the literature.
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Registered trials
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.