Evidence map›Paper›PMID 41460266›Full record

ArticleForensic toxicology2026

Study on the expression changes of hepatic Gluconeogenesis-related proteins induced by insulin Overdose-related liver injury.

Yuhao Yuan, Yiling Li, Jiaxin Zhang, Xiangting Gao, Chen Chen, Zhonghao Yu, Yiwu Zhou

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Article in Forensic toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yuhao Yuan *Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yiling Li *Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jiaxin ZhangDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiangting GaoDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chen ChenDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhonghao YuDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 1259970467@qq.com.
Yiwu ZhouDepartment of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. zhouyiwu@outlook.com.ORCID 0000-0002-6061-6769

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeInsulin overdose severely disrupts hepatic glucose metabolism, leading to toxic changes in the liver that may play an important role in the diagnosis and identification of insulin overdose.

methodsA rat model of insulin overdose was established in this study. ALT and AST levels were measured to assess liver function. Hematoxylin and eosin, oil red O, and periodic acid-Schiff staining were used to evaluate pathological liver injury. Ultrastructural changes in hepatocyte organelles were observed under a transmission electron microscope. The expression levels of liver gluconeogenesis-related proteins, including forkhead box protein O1 (FOXO1) and phosphorylated FOXO1 (p-FOXO1), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase catalytic subunit (G6PC), chromosome region maintenance 1 (CRM1), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein (14-3-3), were detected in the rat model and human autopsy liver tissues using immunohistochemistry and immunofluorescence.

resultsThe insulin overdose group showed elevated ALT/AST, hepatocyte fatty degeneration, glycogen depletion, mitochondrial swelling, and cristae loss. The recovery group exhibited milder fatty changes, glycogen accumulation, and restored mitochondria. Insulin overdose increased hepatic p-FOXO1, CRM1, and 14-3-3 expression but decreased PEPCK and G6PC. FOXO1 shifted from nuclear to cytoplasmic localization in overdose groups, with partial nuclear recovery post-recovery.

conclusionInsulin overdose leads to hypoglycemia, which in turn causes hepatocyte damage. Insulin overdose promotes the nuclear translocation of FOXO1 protein in hepatocytes, and this process shows high reproducibility in human cases of fatal insulin overdose. The coordinated changes in these indicators have significant value in detecting and diagnosing fatal cases of insulin overdose.

Indexed as

Chemical and Drug Induced Liver InjuryDrug OverdoseGluconeogenesisHypoglycemic AgentsInsulinLiver14-3-3 ProteinsAlanine TransaminaseAnimalsAspartate AminotransferasesDisease Models, AnimalForkhead Box Protein O1Glucose-6-PhosphataseHepatocytesHumansImmunohistochemistry14-3-3 ProteinsAlanine TransaminaseAspartate AminotransferasesForkhead Box Protein O1Foxo1 protein, ratGlucose-6-PhosphataseHypoglycemic AgentsInsulinIntracellular Signaling Peptides and ProteinsNerve Tissue ProteinsPck1 protein, ratPhosphoenolpyruvate Carboxykinase (ATP)Phosphoenolpyruvate Carboxykinase (GTP)FOXO1GluconeogenesisInsulin overdoseLiver injury

Identifiers

PMID41460266

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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.