Evidence map›Paper›PMID 40089682›Full record

ArticleBMC pregnancy and childbirth2025

Insulin resistance-induced mitochondrial dysfunction and pyroptosis in trophoblasts: protective role of metformin.

Runyu Du, Yu Bai, Ling Li, Ying Shao, Na Wu

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Article in BMC pregnancy and childbirth, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

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

5 authors.

Runyu DuDepartment of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Yu BaiDepartment of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Ling LiDepartment of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Ying ShaoDepartment of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Na WuDepartment of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, China. 20112246@cmu.edu.cn.

Funding

Clinical Research Project of the Liaoning Diabetes Medical Nutrition Prevention Society LNSTNBYXYYFZXH-RS01BClinical Research Project of the Liaoning Diabetes Medical Nutrition Prevention Society LNSTNBYXYYFZXH-RS02ANational Natural Science Foundation of China 81700706National Natural Science Foundation of China 82200930National Natural Science Foundation of China 82300933Science Foundation of the Liaoning Department of Science and Technology 2023JH2/101700125Science Foundation of the Liaoning Department of Science and Technology 2024JH2/102600326
6 · The paper itself

Abstract

backgroundGestational diabetes mellitus (GDM) affects up to 14% of pregnancies globally, with insulin resistance (IR) playing a critical but often underappreciated role in its pathogenesis. Yet the specific impact of insulin at IR levels on mitochondrial function and pyroptosis in first-trimester trophoblasts remains unclear. Metformin use in GDM pregnancies is rising, but its impact on placental mitochondrial function is uncertain. This study aimed to investigate the impact of IR, a key feature of GDM, on mitochondrial dysfunction and pyroptosis in trophoblasts and to evaluate the protective effects of metformin.

methodsDual staining assays using TUNEL and caspase-1, and enzyme-linked immunosorbent assay were conducted to assess pyroptosis and pyroptosis-related inflammatory markers in placentas from 42 GDM patients and 39 controls. In vitro, HTR-8/SVneo trophoblast cells were treated with IR-level insulin concentrations, and a concentration gradient of metformin to evaluate the mitochondrial damage, pyroptosis, and cell viability.

resultsThere was a significant increase in pyroptosis in GDM placenta, as well as pyroptosis-related inflammatory markers, IL-1β and IL-18. Placental IL-1β and IL-18 levels were strongly correlated with IR indices, especially in GDM cases. Moreover, IR-level insulin concentrations induced mitochondrial dysfunction and activated the NLRP3 inflammasome, triggering pyroptosis in HTR-8/SVneo trophoblasts. Metformin, particularly at therapeutic doses (10-100 µM), mitigated IR-induced mitochondrial damage by promoting mitochondrial biogenesis and reducing pyroptosis via suppressing the ROS/TXNIP/NLRP3 pathway. Metformin-treated cells exhibited enhanced mitochondrial respiration, restored membrane potential homeostasis, and reduced oxidative stress.

conclusionIR, independent of hyperglycemia, drives placental inflammation and trophoblastic injury via pyroptosis. Targeting the ROS/TXNIP/NLRP3 pathway with metformin or other therapeutic agents offers potential therapeutic value in managing IR-related complications in GDM.

Indexed as

Diabetes, GestationalHypoglycemic AgentsInsulin ResistanceMetforminMitochondriaPyroptosisTrophoblastsAdultCase-Control StudiesFemaleHumansInterleukin-18Interleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinPlacentaPregnancyHypoglycemic AgentsInterleukin-18Interleukin-1betaMetforminNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanGestational diabetes mellitusHyperinsulinemiaInsulin resistanceMetforminMitochondriaPyroptosis

Identifiers

PMID40089682
PMCPMC11910837

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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Registered trials

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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.