Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug;59(8):1001-1009.
doi: 10.1007/s00592-022-01892-1. Epub 2022 Apr 23.

Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity

Sheng-Chiang Su  1   2 , Yi-Jen Hung  2   3 , Fu-Huang Lin  4 , Chang-Hsun Hsieh  2 , Chieh-Hua Lu  2 , Chu-Yen Chien  1 , Ying-Chen Chen  2 , Peng-Fei Li  2 , Feng-Chih Kuo  2 , Jhih-Syuan Liu  2 , Nain-Feng Chu  2 , Chien-Hsing Lee  5   6   7
Affiliations

Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity

Sheng-Chiang Su et al. Acta Diabetol. 2022 Aug.

Abstract

Aims: Endoplasmic reticulum (ER) stress is associated with obesity and type 2 diabetes mellitus (T2DM) and increasing evidence demonstrates that some ER stress markers can represent the severity of metabolic dysfunction in either cellular or animal models. However, no appropriate molecule has been identified to demonstrate these relationships in clinical practice.

Methods: To determine whether the serum level of the ER chaperone, protein disulfide isomerase family A, member 4 (PDIA4), is associated with type 2 diabetes mellitus, obesity, and insulin sensitivity, we conducted a cross-sectional study for which a total of 553 adults, including 159 with normal glucose tolerance (NGT), 169 with prediabetes (Pre-DM), and 225 with newly diagnosed T2DM, were recruited.

Results: Serum PDIA4 levels were significantly higher in patients with T2DM than in those with NGT (P < 0.001), even after adjustment for potential confounders. These levels correlated positively with fasting plasma glucose, BMI, waist circumference as well as high-sensitivity C-reactive protein levels, and negatively and strongly correlated with insulin sensitivity. In a multivariate logistic regression analysis, higher serum PDIA4 concentration was observed to be significantly associated with an increased risk of T2DM.

Conclusions: Our findings provide new mechanistic insights linking ER stress, T2DM, insulin sensitivity, and obesity, which may, in part, account for the ER chaperone properties associated with PDIA4. The results suggest that PDIA4 may serve as a potential instigator of and a putative therapeutic target for T2DM.

Keywords: ER stress; PDIA4; T2DM.

PubMed Disclaimer

References

    1. Gómez-Ambrosi J, Catalán V, Rodríguez A et al (2014) Increased cardiometabolic risk factors and inflammation in adipose tissue in obese subjects classified as metabolically healthy. Diabetes Care 37:2813–2821. https://doi.org/10.2337/dc14-0937 - DOI - PubMed
    1. Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846. https://doi.org/10.1038/nature05482 - DOI - PubMed
    1. Kratochvílová K, Moráň L, Paďourová S et al (2016) The role of the endoplasmic reticulum stress in stemness, pluripotency and development. Eur J Cell Biol 95:115–123. https://doi.org/10.1016/j.ejcb.2016.02.002 - DOI - PubMed
    1. Cao SS, Kaufman RJ (2014) Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid Redox Signal 21:396–413. https://doi.org/10.1089/ars.2014.5851 - DOI - PubMed - PMC
    1. Jansen G, Määttänen P, Denisov AY et al (2012) An interaction map of endoplasmic reticulum chaperones and foldases. Mol Cell Proteom 11:710–723. https://doi.org/10.1074/mcp.M111.016550 - DOI

LinkOut - more resources