Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00138)
Name
Gestational diabetes
ICD
ICD-11: JA63
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Gestational diabetes mellitus [ICD-11: JA63]
Responsed Regulator NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
mTOR signaling pathway hsa04150
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model HTR-8/SVneo cells Normal Homo sapiens CVCL_7162
pTr2 cells Normal Sus scrofa CVCL_YB18
Response regulation Upregulated SIRT3-enhanced autophagy activation by promoting AMPK-mTOR pathway and decreasing GPX4 level to induce ferroptosis in trophoblastic cells. SIRT3 deficiency was resistant to high glucose- and erastin-induced autophagy-dependent ferroptosis and is, therefore, a potential therapeutic approach for treating gestational diabetes mellitus (GDM).
Unspecific Target
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Gestational diabetes [ICD-11: JA63]
Responsed Regulator Adiponectin (ADIPOQ) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HTR-8/SVneo cells Normal Homo sapiens CVCL_7162
In Vivo Model
Mice in STZ, HFD + STZ, and HFD/ADN + STZ group were intraperitoneally injected with STZ 40 mg/kg (STZ dissolved in 0.1 mol/L citric acid/sodium citrate buffer) daily for 3 consecutive days and the criteria for successful modeling of GDM were fasting blood glucose >=11.1 mmol/L or random blood glucose >=16.7 mmol/L 72 h after STZ injection.

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Response regulation ADPN (ADIPOQ) ameliorated placental injury in gestational diabetes (GDM) by correcting fatty acid oxidation/peroxide imbalance-induced ferroptosis via restoration of CPT-1 activity.
References
Ref 1 SIRT3 deficiency is resistant to autophagy-dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels. J Cell Physiol. 2020 Nov;235(11):8839-8851. doi: 10.1002/jcp.29727. Epub 2020 Apr 24.
Ref 2 Adiponectin ameliorates placental injury in gestational diabetes mice by correcting fatty acid oxidation/peroxide imbalance-induced ferroptosis via restoration of CPT-1 activity. Endocrine. 2022 Mar;75(3):781-793. doi: 10.1007/s12020-021-02933-5. Epub 2021 Dec 2.