Metabolic disorders that include diabetes mellitus present significant challenges for
maintaining the welfare of the global population. Metabolic diseases impact all systems of the
body and despite current therapies that offer some protection through tight serum glucose control,
ultimately such treatments cannot block the progression of disability and death realized with
metabolic disorders. As a result, novel therapeutic avenues are critical for further development to
address these concerns. An innovative strategy involves the vitamin nicotinamide and the pathways
associated with the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae)
(SIRT1), the mechanistic target of rapamycin (mTOR), mTOR Complex 1 (mTORC1),
mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and clock genes. Nicotinamide
maintains an intimate relationship with these pathways to oversee metabolic disease and improve
glucose utilization, limit mitochondrial dysfunction, block oxidative stress, potentially function
as antiviral therapy, and foster cellular survival through mechanisms involving autophagy.
However, the pathways of nicotinamide, SIRT1, mTOR, AMPK, and clock genes are complex and
involve feedback pathways as well as trophic factors such as erythropoietin that require a careful
balance to ensure metabolic homeostasis. Future work is warranted to gain additional insight into
these vital pathways that can oversee both normal metabolic physiology and metabolic disease.
Keywords: Alzheimer's disease, AMP activated protein kinase (AMPK), autophagy, apoptosis, circadian rhythm, clock genes,
coronavirus disease 2019 (COVID-19), dementia, diabetes mellitus, erythropoietin, mechanistic target of rapamycin (mTOR),
metformin, oxidative stress, poly-ADP-ribose polymerase (PARP), SARS-CoV-2, silent mating type information regulation 2
homolog 1 (Saccharomyces cerevisiae) (SIRT1), sirtuin, stem cells.
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