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

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.

• Authors: Sheng-Chiang Su, Yi-Jen Hung, Fu-Huang Lin, Chang-Hsun Hsieh, Chieh-Hua Lu, Chu-Yen Chien, Ying-Chen Chen, Peng-Fei Li, Feng-Chih Kuo, Jhih-Syuan Liu, Nain-Feng Chu, Chien-Hsing Lee
• Journal: Acta diabetologica (Acta Diabetol) Vol. 59 Issue 8 Pg. 1001-1009 (Aug 2022) ISSN: 1432-5233 [Electronic] Germany
• PMID: 35460376 (Publication Type: Journal Article)
• Copyright: © 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.

Chemical References

• Blood Glucose
• PDIA4 protein, human
• Protein Disulfide-Isomerases

Topics

• Blood Glucose (metabolism)
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (complications)
• Family
• Humans
• Insulin Resistance
• Obesity (complications)
• Protein Disulfide-Isomerases (blood)