ArticlePloS one2015
Zinc-α2-Glycoprotein Modulates AKT-Dependent Insulin Signaling in Human Adipocytes by Activation of the PP2A Phosphatase.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis.Reviews in endocrine & metabolic disorders · 2020Pooled it
- Zinc and Adipose Organ Dysfunction: Molecular Insights into Obesity and Metabolic Disorders.Current nutrition reports · 2025Review
- Serum Zinc-Alpha-2 Glycoprotein and Zinc Levels and Their Relationship with Insulin Resistance and Biochemical Parameters in Overweight and Obese Children.Biological trace element research · 2025Article
- Circular RNA circIGF1R controls cardiac fibroblast proliferation through regulation of carbohydrate metabolism.Scientific reports · 2025Article
- Acute Downregulation of Zinc α2-Glycoprotein: Evidence from Human and HepG2 Cell Studies.International journal of molecular sciences · 2025Article
- Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-β and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model.Tissue engineering and regenerative medicine · 2024Article
- CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Zinc.Advances in food and nutrition research · 2021Review
- Adipokines in the Skin and in Dermatological Diseases.International journal of molecular sciences · 2020Review
- The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity.Journal of diabetes research · 2020Article
- Low Serum ZAG Levels Correlate With Determinants of the Metabolic Syndrome in Chinese Subjects.Frontiers in endocrinology · 2020Article
- Expression and Function of Zinc-α2-Glycoprotein.Neuroscience bulletin · 2019Review
- Changes in zinc-α2-glycoprotein (ZAG) plasma concentrations pre and post Roux-En-Y gastric bypass surgery (RYGB) or a very low calorie (VLCD) diet in clinically severe obese patients: Preliminary Study.Integrative obesity and diabetes · 2017Article
- Zinc and diabetes mellitus: understanding molecular mechanisms and clinical implications.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2015Review
- Zinc Alpha-2 Glycoprotein, Acylated Ghrelin, and Zinc Levels in Prediabetics.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveEvidence from mouse models suggests that zinc-α2-glycoprotein (ZAG) is a novel anti-obesity adipokine. In humans, however, data are controversial and its physiological role in adipose tissue (AT) remains unknown. Here we explored the molecular mechanisms by which ZAG regulates carbohydrate metabolism in human adipocytes.
methodsZAG action on glucose uptake and insulin action was analyzed. β1 and β2-adrenoreceptor (AR) antagonists and siRNA targeting PP2A phosphatase were used to examine the mechanisms by which ZAG modulates insulin sensitivity. Plasma levels of ZAG were measured in a lean patient cohort stratified for HOMA-IR.
resultsZAG treatment increased basal glucose uptake, correlating with an increase in GLUT expression, but induced insulin resistance in adipocytes. Pretreatment of adipocytes with propranolol and a specific β1-AR antagonist demonstrated that ZAG effects on basal glucose uptake and GLUT4 expression are mediated via β1-AR, whereas inhibition of insulin action is dependent on β2-AR activation. ZAG treatment correlated with an increase in PP2A activity. Silencing of the PP2A catalytic subunit abrogated the negative effect of ZAG on insulin-stimulated AKT phosphorylation and glucose uptake but not on GLUT4 expression and basal glucose uptake. ZAG circulating levels were unchanged in a lean patient cohort stratified for HOMA-IR. Neither glucose nor insulin was associated with plasma ZAG.
conclusionsZAG inhibits insulin-induced glucose uptake in human adipocytes by impairing insulin signaling at the level of AKT in a β2-AR- and PP2A-dependent manner.
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