New Insights for Oxidative Stress and Diabetes Mellitus

Table 1

Targeting mTOR, SIRT1, and WISP1 in Oxidative Stress and DM.

Target	Actions
mTOR	Functions through trophic factors such as EPO to protect vascular cells, promotes neuronal precursors, and blocks retinal degeneration; Functions through metformin during mTOR inhibition and AMPK activity to protect against cardiomyopathy, protect cortical brain tissue, and prevent endothelial senescence; Promotes stem cell development, promotes pancreatic -cell proliferation, and blocks vascular thrombosis
SIRT1	Promotes telomere elongation and genomic stability of induced pluripotent stem cells, prevents apoptosis in endothelial progenitor cells and mesenchymal stem cells, increases lifespan in higher organisms, and preserves angiogenesis; Prevents insulin resistance through fat mobilization, mTOR signaling, and control of cellular inflammation; Increases insulin signaling through PI 3-K and Akt and insulin release in pancreatic cells, promotes autophagy to protect embryonic stem cells during oxidative stress, in conjunction with AMPK activation protects endothelial cells during exposure to oxidized low density lipoproteins that can lead to atherosclerosis
WISP1	During pancreatic regeneration, WISP1 is one of several genes that are over-expressed, suggesting that WISP1 may be reparative during DM; Promotes vascular smooth muscle proliferation that may be important for tissue repair, activates PI 3-K and Akt pathways to protect cells against oxidative stress and programmed cell death; Oversees vascular senescence, modulates AMPK activity that may be sometimes detrimental, maintains the integrity of SIRT1 and prevent its degradation during oxidative stress

AMPK: AMP activated protein kinase; Akt: protein kinase B; EPO: erythropoietin; mTOR: mechanistic target of rapamycin; PI 3-K: phosphoinositide 3 –kinase; SIRT1: silent mating type information regulation 2 homolog 1 (S. cerevisiae); WISP1: wnt1 inducible signaling pathway protein 1.