We found that expression of both Sirt6 and Sirt3 was reduced in cardiomyocytes treated with palmitate and in hearts of mice fed with a high-fat, high-sucrose (HF-HS) diet to develop obesity and diabetes.
Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far.
In this review, we are primarily concerned with exploring the latest advances in understanding SIRT6 and how it can alter the course of several life-threatening diseases such as processes related to aging, cancer, neurodegenerative diseases, heart disease, and diabetes (SIRT6 has also shown to be involved in liver disease, inflammation, and bone-related issues) and any recent promising pharmacological investigations or potential therapeutics that are of interest.
In contrast, a recent study showed that a synthetic inhibitor of SIRT6 improved glucose tolerance in a type 2 diabetes mouse model, associated with increased glycolysis and the expression of glucose transporter GLUT-1 and 4 in skeletal muscle, providing proof-of-concept evidence of SIRT6 inhibition as a treatment for diabetes.