Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

Abstract

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.

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

“…Autophagosomes then combine with lysosomes for degradation and recycling (13, 97). Microautophagy is the invagination of the lysosomal membranes for the sequestration and digestion of cytoplasmic components (5). Chaperone-mediated autophagy (58) relies upon cytosolic chaperones to transport cytoplasmic components across lysosomal membranes (98).…”

“…In addition, the number of individuals over the age of sixty-five has doubled during the previous fifty years (3). It is expected that the number of elderly individuals in large developing countries such as India and China also will increase from five percent to ten percent over the next several decades (4, 5). There are a number of reasons that may account for the increased lifespan, but improvements in effective treatments for multiple disorders (6–10) and broader access to preventive care are believed to have contributed to the increased life span of the world’s population.…”

“…Another eight million individuals also have metabolic disorders but remain undiagnosed at present (23–25). Impaired glucose tolerance in the young (5, 26) and the presence of obesity increases the risk of developing DM in these individuals (19). …”

FoxO Transcription Factors and Regenerative Pathways in Diabetes Mellitus

“…The incidence of DM is increasing throughout the world (71). Approximately 350 million individuals currently have DM, but the World Health Organization estimates that DM will be the seventh leading cause of death by the year 2030 (72).…”

“…During macroautophagy, cytoplasmic proteins and organelles are sequestered into autophagosomes and then combined with lysosomes for degradation and are recycled for future cellular processes (32, 46, 71, 118, 119). Under some circumstances, autophagy may protect cells during DM by eliminating non-functional organelles and may be less of a significant mediator of cell injury (120).…”