ArticleMolecular endocrinology (Baltimore, Md.)2015
PGRN induces impaired insulin sensitivity and defective autophagy in hepatic insulin resistance.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- Progranulin serum levels in human kidney transplant recipients: A longitudinal study.PloS one · 2018Trial
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Effects of Progranulin Deficiency on Inflammation and Fibrosis in the Kidneys and Liver of Diabetic Mice Fed a High-Fat Diet.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Grna knockout resists HFD-induced obesity and leads to impaired liver development in zebrafish.Fish physiology and biochemistry · 2026Article
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Frontiers in cell and developmental biology · 2022Review
- Increased Fat Taste Preference in Progranulin-Deficient Mice.Nutrients · 2021Article
- Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease.Journal of molecular medicine (Berlin, Germany) · 2021Article
- TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity.The Journal of clinical investigation · 2021Article
- Serum Progranulin As a Risk Predictor in Patients with Acute Myocardial Infarction.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Differential organ-specific inflammatory response to progranulin in high-fat diet-fed mice.Scientific reports · 2021Article
- In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Progranulin modulates cartilage-specific gene expression via sirtuin 1-mediated deacetylation of the transcription factors SOX9 and P65.The Journal of biological chemistry · 2020Article
- Approaches to develop therapeutics to treat frontotemporal dementia.Neuropharmacology · 2020Review
- Progranulin Regulates Inflammation and Tumor.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
- Progranulin alleviates podocyte injury via regulating CAMKK/AMPK-mediated autophagy under diabetic conditions.Journal of molecular medicine (Berlin, Germany) · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progranulin (PGRN) has recently emerged as an important regulator for glucose metabolism and insulin sensitivity. However, the underlying mechanisms of PGRN in the regulation of insulin sensitivity and autophagy remain elusive. In this study, we aimed to address the direct effects of PGRN in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. We found that mice treated with PGRN for 21 days exhibited the impaired glucose tolerance and insulin tolerance and hepatic autophagy imbalance as well as defective insulin signaling. Furthermore, treatment of mice with TNF receptor (TNFR)-1 blocking peptide-Fc, a TNFR1 blocking peptide-Fc fusion protein to competitively block the interaction of PGRN and TNFR1, resulted in the restoration of systemic insulin sensitivity and the recovery of autophagy and insulin signaling in liver. Consistent with these findings in vivo, we also observed that PGRN treatment induced defective autophagy and impaired insulin signaling in hepatocytes, with such effects being drastically nullified by the addition of TNFR1 blocking peptide -Fc or TNFR1-small interference RNA via the TNFR1-nuclear factor-κB-dependent manner, indicating the causative role of PGRN in hepatic insulin resistance. In conclusion, our findings supported the notion that PGRN is a key regulator of hepatic insulin resistance and that PGRN may mediate its effects, at least in part, by inducing defective autophagy via TNFR1/nuclear factor-κB.
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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.