Hypoxia-reoxygenation treatment attenuates gestational diabetes mellitus

Abstract

Background: Oxidative stress leads to insulin resistance and gestational diabetes mellitus (GDM). The nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) signaling is an important anti-oxidative stress pathway, which can be activated by hypoxia‑reoxygenation (H/R) treatment. We aimed to demonstrate the effects of H/R treatment on GDM symptoms as well as reproductive outcomes. Methods: Pregnant C57BL/KsJ db/+ mice were used as a genetic GDM model. Plasma insulin and other biochemical indexes of plasma, insulin sensitivity, glucose intolerance, blood glucose and liver biochemical indexes were evaluated. Protein abundance of HO-1 and Nrf2 were assessed with Western blot. Results: H/R treatment markedly ameliorated β-cell insufficiency and glucose intolerance, suppressed oxidative stress in vivo, stimulated the activities of anti-oxidant enzymes, and led to improved reproductive outcomes. The beneficial effects of H/R treatment were mechanistically mediated via the restoration of Nrf2/HO-1 anti-oxidant signaling pathway in the liver of GDM mice. Conclusion: Our study, for the first time, suggests that H/R treatment is a potentially novel therapeutic approach against GDM symptoms, by activating the Nrf2/HO-1 signaling pathway and inhibiting oxidative stress.

Hypoxia ameliorates maternal diet‐induced insulin resistance during pregnancy while having a detrimental effect on the placenta

“…It has been shown earlier in a diet‐induced IR model that an exercise‐mediated improvement in maternal insulin sensitivity rescued the insulin sensitivity of her male offspring, indicating that hyperinsulinemia is a key programming factor, and therefore an important interventional target, during obese pregnancy (Fernandez‐Twinn et al, 2017 ). Moreover, in a genetic GDM model involving db/+ mice, hypoxia/reoxygenation treatment (1 h 6% O 2 followed by reoxygenation at 21% O 2 once a day), markedly ameliorated β‐cell insufficiency and glucose intolerance, suppressed oxidative stress and stimulated antioxidant enzymes, leading to improved reproductive outcomes (Hou et al, 2021 ). The sustained moderate environmental hypoxia (15% O 2 ) used in the present work significantly improved the glucose tolerance and HOMA‐IR scores of the dams with diet‐induced IR compared with normoxia, even maintaining the levels seen in the NC controls, which could indicate beneficial effects on maternal metabolism.…”

Protective effect of sinomenine against inflammation and oxidative stress in gestational diabetes mellitus in female rats via TLR4/MyD88/NF‐κB signaling pathway

“…In previous investigations, oxidative stress was found to be an essential factor in the development of gestational diabetes. Clinical and experimental investigations showed that different reasons related to hyperglycemia, which leads to ROS formation through various biochemical pathways such as glycation of protein and glucose autoxidation (Hou et al, 2021).…”

Myeloperoxidase G-463A and CYBA C242T genetic variants in gestational diabetes mellitus

“…Oxidative stress plays an important part in the pathophysiology of GDM ( 5 , 23 , 24 , 25 , 26 , 27 ). Nevertheless, it remains unclear whether the SNPs CYBA C242T and MPO G-463A are associated with GDM.…”