T1DM causes hyperglycemia due to B-cell immune mediated destruction which results in insulinopenia followed by hyperglycemia. Hyperglycemia induced ROS triggers a vicious cycle of impaired redox balance, as far I know the main mechanisms which hyperglycemia can induce ROS production occurs in the cellular milieu such as mitochondrial electron transport chain (ETC) and polyol pathway, etc. As we define this impaired redox balance state in the pathogenesis of hyperglycemia:
So what is the missing key when there is a lower intracellular concentration of glucose even compared to normal condition due to insulinopenia, for over generation of ROS more than antioxidant defense system capacity in T1DM or mimicked condition by STZ?
Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Several signaling pathways can be altered by having hyperglycemia in different tissues, producing oxidative stress, the formation of advanced glycation end products (AGEs), as well as the secretion of the pro-inflammatory cytokines and cellular death (pathological autophagy and/or apoptosis). However, the signaling pathways that are directly triggered by hyperglycemia appear to have a pivotal role in diabetic complications due to the production of reactive oxygen species (ROS), oxidative stress, and cellular death. The potential targets needing for control are the signaling pathways of DAG—PKC—NADPH-oxidase, as welle as mTORC1 pathway step-by-step, causing the downregulation of ROS generation, oxidative stress, and, consequently, cellular death.
Lipotoxicity and glucotoxicity are key pathways to ROS generation
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