Elevated circulating GPHB5 levels in women with insulin resistance and polycystic ovary syndrome: A cross-sectional study and multiple intervention studies
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Objective: GPHB5 has been found to be associated with glucose and lipid metabolism in animal studies. However, the association of GPHB5 with IR and metabolic disorders remains unknown, and there is a lack of research in humans. Our aim in this study was to investigate the relationship between circulating GPHB5 and metabolic disorders in humans. Methods: Bioinformatics analysis was performed to understand the relationship between GPHB5 and metabolic disorders. GPHB5 mRNA expression in mice and rats was determined using RT-qPCR. Circulating GPHB5 concentrations were measured with an ELISA kit. EHC and OGTT were performed in humans. Results: Bioinformatics analysis shows that GPHB5 is associated with metabolic disorders and PCOS. GPHB5 mRNA expression levels in the metabolic-related tissues of HFD-fed mice, db/db and ob/ob mice, and PCOS rats were significantly higher than those of WT mice or rats. In human studies, we find that circulating GPHB5 levels were significantly higher in women with IR and PCOS. GPHB5 levels were positively correlated with age, BMI, WHR, BP, FBG, 2 h-BG, FIns, 2 h-Ins, TC, LDL-C, HbA1c, and FFA, but negatively correlated with adiponectin. Furthermore, GPHB5 was positively correlated with DHEAS and FAI, while negatively correlated with SHBG, FSH, SHBG and FSH. The increased GPHB5 concentration was related to IR and PCOS. After the treatment of metformin, GLP-1RA (Lira), and TZDs, circulating GPHB5 levels were decreased. Conclusions: Our results reveal that circulating GPHB5 could be a biomarker and potential therapeutic target for IR and PCOS in women.
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While GLP-1RAs may not outperform metformin in managing hormone levels, they are still beneficial in populations not already treated with metformin.
“This suggests that while GLP-1RAs may not outperform metformin in managing hormone levels, they are still beneficial in populations not already treated with metformin23–26.”
From Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials (2025) · cites this paper as [25]
The Results (Table 6; page unavailable) show improvements in some hormone measures after GLP-1RA treatment in women with PCOS, supporting a benefit. They do not establish that GLP-1RAs fail to outperform metformin: testosterone fell significantly with GLP-1RA but not metformin, while other hormone results were mixed. The Drug intervention study section describes separate treatment groups but does not establish participants’ prior metformin use. (LLM, conf=0.84)
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- Authors
- Wang, Y., Xiang, T., Xia, X., Zhang, H., Geng, S., Yang, G., Qiu, S., He, Y., Liu, R., Li, L., Liu, H., Li, K., Zhang, L., Liang, Z., & He, J.
- Affiliations
- Second Affiliated Hospital of Chongqing Medical University (CN)
- First People's Hospital of Chongqing (CN)
- Chongqing Dazu District People's Hospital (CN)
- Chongqing Medical University (CN)
- University of Mississippi Medical Center (US)
- Corresponding author
- Liang, Zerong
- He, Jianguo
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2022-12-08
- Volume
- 13
- Pages
- 1010714-1010714
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC9772026
- OpenAlex
- W4311850395
- Cited by
- 5
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1
- FWCI
- 0.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chongqing Municipal Health Commission
- Chongqing Municipal Education Commission
- Natural Science Foundation of Chongqing
- China Postdoctoral Science Foundation
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin resistance, polycystic ovary syndrome, circulating biomarkers, metabolic disorders, glucose metabolism, lipid metabolism, adiponectin, metformin, GLP-1 receptor agonists, thiazolidinediones, high-fat diet, type 2 diabetes
- MeSH terms
- Animals, Cross-Sectional Studies, Female, Follicle Stimulating Hormone, Glycoproteins, Humans, Insulin Resistance, Polycystic Ovary Syndrome, RNA, Messenger, Mice, Rats
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