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

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Diabetes Mellitus, Type 2*/complications ; Insulin Resistance* ; Obesity*/complications ; Protein Disulfide-Isomerases*/blood; Blood Glucose/metabolism ; Cross-Sectional Studies ; Family ; Humans

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.
(© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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MOST 105-2314-B-016 -040 -MY3 Ministry of Science and Technology, Taiwan; MOST 108-2314-B-016 -033 -MY2 Ministry of Science and Technology, Taiwan; MOST 108-2314-B-016 -019 -MY3 Ministry of Science and Technology, Taiwan; TSGH-C106-006-S02 Tri-Service General Hospital; TSGH-C107-006-006-S02 Tri-Service General Hospital; TSGH-C108-005-006-006-S02 Tri-Service General Hospital; MAB-105-084 Tri-Service General Hospital; MAB-108-046 Tri-Service General Hospital; TSGH-D-110058 Tri-Service General Hospital; TSGH-D-111115 Tri-Service General Hospital

Keywords: ER stress; PDIA4; T2DM

0 (Blood Glucose)
EC 5.3.4.1 (PDIA4 protein, human)
EC 5.3.4.1 (Protein Disulfide-Isomerases)

Date Created: 20220423 Date Completed: 20220701 Latest Revision: 20220705

20240829

10.1007/s00592-022-01892-1

35460376