Zinc-α2-Glycoprotein Is Associated With Insulin Resistance in Humans and Is Regulated by Hyperglycemia, Hyperinsulinemia, or Liraglutide Administration
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OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has been proposed to play a role in the pathogenesis of insulin resistance. Previous studies in humans and in rodents have produced conflicting results regarding the link between ZAG and insulin resistance. The objective of this study was to examine the relationships between ZAG and insulin resistance in cross-sectional and interventional studies. RESEARCH DESIGN AND METHODS: Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial. RESULTS: Circulating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA1c, and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels. CONCLUSIONS: We conclude that ZAG may be an adipokine associated with insulin resistance.
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Three clear outliers were identified; one was corrected and no longer an outlier, and the other two were excluded from the meta-analysis.
“This approach identified three clear outliers (Micic et al., 2007;Yang et al., 2013;Wu et al., 2014).”
From Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic–hyperinsulinaemic clamp studies (2016) · cites this paper as Yang et al., 2013
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- Authors
- Yang, M., Liu, R., Li, S., Luo, Y., Zhang, Y., Zhang, L., Liu, D., Wang, Y., Xiong, Z., Boden, G., Chen, S., Li, L., & Yang, G.
- Affiliations
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
- Temple University (US)
- Corresponding author
- Chen, Shirong
- Li, Ling
- Yang, Gangyi
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2013-04-13
- Volume
- 36
- Issue
- 5
- Pages
- 1074-1082
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3631846
- OpenAlex
- W2109300793
- Cited by
- 100
- References
- 27
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 13 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 7 · 2013: 1
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- zinc-alpha2-glycoprotein, insulin resistance, type 2 diabetes, impaired glucose tolerance, polycystic ovary syndrome, adipokines, liraglutide, GLP-1 receptor agonists, adipose tissue, adiponectin, hyperinsulinemia, hyperglycemia, body mass index
- MeSH terms
- Liraglutide, Zn-Alpha-2-Glycoprotein, Adult, Aged, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Hyperinsulinism, Insulin Resistance, Male, Middle Aged, Polycystic Ovary Syndrome, Seminal Plasma Proteins, Glucagon-Like Peptide 1, Adipokines
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