ArticlePloS one2012
Diabetes-induced hepatic pathogenic damage, inflammation, oxidative stress, and insulin resistance was exacerbated in zinc deficient mouse model.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 102 citations in OpenAlex.
- Fyn Kinase: A Potential Target in Glucolipid Metabolism and Diabetes Mellitus.Current issues in molecular biology · 2025Review
- A Comprehensive Review of Naringenin, a Promising Phytochemical with Therapeutic Potential.Journal of microbiology and biotechnology · 2024Review
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- GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model.International journal of molecular sciences · 2024Review
- Marginal Maternal Zinc Deficiency Produces Liver Damage and Altered Zinc Transporter Expression in Offspring Male Rats.Biological trace element research · 2024Article
- Relationship between ferroptosis and healing of diabetic foot ulcer: a prospective clinical study.Frontiers in endocrinology · 2024Article
- Zinc: a potential star for regulating peritoneal fibrosis.Frontiers in pharmacology · 2024Review
- Effect of zinc oxide nanocomposite and ginger extract on lipid profile, glucose, pancreatic tissue and expression of Gpx1 and Tnf-α genes in diabetic rat model.Molecular biology reports · 2023Article
- Mango ginger (Food science & nutrition · 2023Article
- Combined resveratrol and vitamin D treatment ameliorate inflammation-related liver fibrosis, ER stress, and apoptosis in a high-fructose diet/streptozotocin-induced T2DM model.Histochemistry and cell biology · 2022Article
- Sulforaphane inhibits angiotensin II-induced cardiomyocyte apoptosis by acetylation modification of Nrf2.Aging · 2022Article
- Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy.Nutrition & diabetes · 2022Article
- Alteration in Gut Microbiota Associated with Zinc Deficiency in School-Age Children.Nutrients · 2022Article
- Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury-Insight into Oxidative Injury/Inflammation/Apoptosis Modulation.Life (Basel, Switzerland) · 2022Article
- Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview.International journal of endocrinology · 2022Review
- Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes.Scientific reports · 2021Article
- 4-Hydroxy-2-nonenal, a lipid peroxidation product, as a biomarker in diabetes and its complications: challenges and opportunities.Free radical research · 2021Review
- Zinc Supplementation Prevented Type 2 Diabetes-Induced Liver Injury Mediated by the Nrf2-MT Antioxidative Pathway.Journal of diabetes research · 2021Article
- Modulation of the Wound Healing through Noncoding RNA Interplay and GSK-3International journal of genomics · 2021Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesZinc (Zn) deficiency often occurs in the patients with diabetes. Effects of Zn deficiency on diabetes-induced hepatic injury were investigated.
methodsType 1 diabetes was induced in FVB mice with multiple low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with and without Zn chelator, N,N,N',N'-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN), at 5 mg/kg body-weight daily for 4 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level and liver histopathological and biochemical changes.
resultsHepatic Zn deficiency (lower than control level, p<0.05) was seen in the mice with either diabetes or TPEN treatment and more evident in the mice with both diabetes and TPEN. Zn deficiency exacerbated hepatic injuries, shown by further increased serum ALT, hepatic lipid accumulation, inflammation, oxidative damage, and endoplasmic reticulum stress-related cell death in Diabetes/TPEN group compared to Diabetes alone. Diabetes/TPEN group also showed a significant decrease in nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and transcription action along with significant increases in Akt negative regulators, decrease in Akt and GSK-3β phosphorylation, and increase in nuclear accumulation of Fyn (a Nrf2 negative regulator). In vitro study with HepG2 cells showed that apoptotic effect of TPEN at 0.5-1.0 µM could be completely prevented by simultaneous Zn supplementation at the dose range of 30-50 µM.
conclusionsZn is required for maintaining Akt activation by inhibiting the expression of Akt negative regulators; Akt activation can inhibit Fyn nuclear translocation to export nuclear Nrf2 to cytoplasm for degradation. Zn deficiency significantly enhanced diabetes-induced hepatic injury likely through down-regulation of Nrf2 function.
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