The mammalian
Sirtuins (SIRT1-7) are an evolutionarily conserved family of
NAD+-dependent deacylase and
mono-ADP-ribosyltransferase.
Sirtuins display distinct subcellular localizations and functions and are involved in cell survival, senescence, metabolism and
genome stability. Among the mammalian
Sirtuins,
SIRT1 and SIRT6 have been thoroughly investigated and have prominent metabolic regulatory roles. Moreover,
SIRT1 and SIRT6 have been implicated in
obesity,
insulin resistance,
type 2 diabetes mellitus (T2DM),
fatty liver disease and
cardiovascular diseases. However, the roles of other
Sirtuins are not fully understood. Recent studies have shown that these
Sirtuins also play important roles in
inflammation,
mitochondrial dysfunction, and energy metabolism.
Insulin resistance is the critical pathological trait of
obesity and
metabolic syndrome as well as the core defect in T2DM. Accumulating clinical and experimental animal evidence suggests the potential roles of the remaining
Sirtuins in the regulation of
insulin resistance through diverse biological mechanisms. In this review, we summarize recent advances in the understanding of the functions of
Sirtuins in various
insulin resistance-associated physiological processes, including
inflammation,
mitochondrial dysfunction, the
insulin signaling pathway,
glucose, and lipid metabolism. In addition, we highlight the important gaps that must be addressed in this field.