Evidence mapPaperPMID 41316343Full record

ArticleNutrition & metabolism2025

The beneficial effect of hepatic ER stress-associated protein PDI on obesity-associated glucose dysregulation.

Da Fang, Xin Yu, Pengzi Zhang, Wenhuan Feng, Ting Hong, Tianwei Gu

Registry-linked trialAbstract read
In one paragraph

Article in Nutrition & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03296605 (Impacts of Bariatric Surgery on Obesity in China), which is not on this map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03296605 enrolling by invitationnot on this map

Impacts of Bariatric Surgery on Obesity in China

TypeobservationalSponsorThe Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolRan2017 to 2025Enrolled150ConditionsObesity
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Da FangDepartment of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321 Zhongshan Road, Nanjing, 210008, China.
Xin YuDepartment of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, No 321 Zhongshan Road, Nanjing, 210008, China.
Pengzi ZhangDepartment of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321 Zhongshan Road, Nanjing, 210008, China.
Wenhuan FengDepartment of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321 Zhongshan Road, Nanjing, 210008, China.
Ting HongDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. Hong.ting@zs-hospital.sh.cn.
Tianwei GuDepartment of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, No 321 Zhongshan Road, Nanjing, 210008, China. gtw0235@163.com.

Funding

China International Medical Foundation No.2023 -N -03 -01Nanjing Health Science and Technology Development Project ZKX22027National Natural Science Foundation of China Grant Awards 82370841National Natural Science Foundation of China Grant Awards 82401007Natural Science Foundation of Jiangsu Province of China BK20240232Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024YFA1307001
6 · The paper itself

Abstract

backgroundThe liver plays critical roles in glucose metabolism regulation. Accumulating evidence supported that endoplasmic reticulum (ER) stress in liver tissue may involve in the development of type 2 diabetes. However, the role of ER stress-associated proteins in diabetes still needs to be clarified.

methodsGenome-wide DNA methylome and proteome in the liver biopsies from patients with or without type 2 diabetes were performed and further validated by pyro-sequencing, real-time PCR and western blots. Circulating protein disulfide isomerase (PDI) levels at baseline and postoperative follow-up were measured by ELISA. The glucose tolerance, metabolic gene expression, glycogen deposition, glycogenesis and ER stress-associated proteins were detected in adeno-associated virus (AAV)-treated high fat-diet (HFD) mice.

resultsBased on methylome and proteome analysis, we identified the hypermethylation of PDI gene in liver biopsies, concomitant with decreased mRNA expression and protein levels in diabetic group compared with non-diabetic group. Circulating PDI levels were lower in patients with diabetes and elevated after metabolic surgery. The decreased PDI expression was correlated with increased gluconeogenesis and reduced glycogen synthesis in human liver tissue. Furthermore, hepatic PDI downregulation aggravated hyperglycemia, whereas PDI overexpression ameliorated glucose intolerance, decreased glycogen deposition and increased glycogenesis in HFD mice.

conclusionsWe identified the beneficial effect of ER stress-associated protein PDI on the regulation of hepatic glucose metabolism, which is expected to be a potential therapeutic target against type 2 diabetes, and provided an important clue for better understanding ER stress in the pathogenesis of diabetes.

trial registrationThe study was registered on ClinicalTrials.gov (NCT03296605).

Indexed as

Glucose metabolismLiverProtein disulfide isomeraseType 2 diabetes

Identifiers

PMID41316343
PMCPMC12661663

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.