According to the World Health Organization, diabetes mellitus (DM) in the year 2030 will be ranked the
seventh leading cause of death in the world. DM impacts all systems of the body with oxidant stress controlling cell fate
through endoplasmic reticulum stress, mitochondrial dysfunction, alterations in uncoupling proteins, and the induction of
apoptosis and autophagy. Multiple treatment approaches are being entertained for DM with Wnt1 inducible signaling
pathway protein 1 (WISP1), mechanistic target of rapamycin (mTOR), and silent mating type information regulation 2
homolog) 1 (S. cerevisiae) (SIRT1) generating significant interest as target pathways that can address maintenance of
glucose homeostasis as well as prevention of cellular pathology by controlling insulin resistance, stem cell proliferation,
and the programmed cell death pathways of apoptosis and autophagy. WISP1, mTOR, and SIRT1 can rely upon similar
pathways such as AMP activated protein kinase as well as govern cellular metabolism through cytokines such as EPO and
oral hypoglycemics such as metformin. Yet, these pathways require precise biological control to exclude potentially
detrimental clinical outcomes. Further elucidation of the ability to translate the roles of WISP1, mTOR, and SIRT1 into
effective clinical avenues offers compelling prospects for new therapies against DM that can benefit hundreds of millions
of individuals throughout the globe.
Keywords: AMPK, apoptosis, autophagy, cardiac, CCN, diabetes mellitus, erythropoietin, forkhead, FoxO, metformin,
nervous system, oxidative stress, mTOR, sirtuins, SIRT1, stem cells, vascular, WISP1, Wnt.
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