ArticleCell cycle (Georgetown, Tex.)2015
Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2α-dependent manner.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Macrophage-Derived Extracellular Vesicles Deliver Progranulin to Alleviate Skin Wound Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.Frontiers in physiology · 2024Review
- Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition.Pediatric research · 2023Article
- Increased Fat Taste Preference in Progranulin-Deficient Mice.Nutrients · 2021Article
- Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model.Metabolites · 2021Article
- Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress.Advances in experimental medicine and biology · 2021Article
- Secreted Chaperones in Neurodegeneration.Frontiers in aging neuroscience · 2020Review
- Progranulin Regulates Inflammation and Tumor.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
- Progranulin attenuates liver fibrosis by downregulating the inflammatory response.Cell death & disease · 2019Article
- Disease-modifying effects of metabolic perturbations in ALS/FTLD.Molecular neurodegeneration · 2018Review
- Blood-borne interleukin-1β acts on the subfornical organ to upregulate the sympathoexcitatory milieu of the hypothalamic paraventricular nucleus.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Progranulin: A key player in autoimmune diseases.Cytokine · 2018Review
- Ginsenoside Rg5 Inhibits Succinate-Associated Lipolysis in Adipose Tissue and Prevents Muscle Insulin Resistance.Frontiers in pharmacology · 2017Article
- New discovery rarely runs smooth: an update on progranulin/TNFR interactions.Protein & cell · 2015Review
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 direct effects of PGRN in vivo and the underlying mechanisms between PGRN and impaired insulin sensitivity are not fully understood. In this study, mice treated with PGRN for 21 d exhibited the impaired glucose tolerance and insulin sensitivity, remarkable ER stress as well as attenuated insulin signaling in liver and adipose tissue but not in skeletal muscle. Furthermore, treatment of mice with phenyl butyric acid (PBA), a chemical chaperone alleviating ER stress, resulted in a significant restoration of systemic insulin sensitivity and recovery of insulin signaling induced by PGRN. Consistent with these findings in vivo, we also observed that PGRN treatment induced ER stress, impaired insulin signaling in cultured hepatocytes and adipocytes, with such effects being partially nullified by blockade of PERK. Whereas PGRN-deficient hepatocytes and adipocytes were more refractory to palmitate-induced insulin resistance, indicating the causative role of the PERK-eIF2α axis of the ER stress response in action of PGRN. Collectively, our findings supported the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by inducing ER stress via the PERK-eIF2α dependent pathway.
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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.