Diabetes Metab J.  2013 Oct;37(5):315-325. 10.4093/dmj.2013.37.5.315.

SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential

• Kitada M
• Koya D

• KMID: 1965977
• DOI: http://doi.org/10.4093/dmj.2013.37.5.315

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) has been increasing worldwide. Therefore, a novel therapeutic strategy by which to prevent T2DM is urgently required. Calorie restriction (CR) can retard the aging processes, and delay the onset of numerous age-related diseases including diabetes. Metabolic CR mimetics may be therefore included as novel therapeutic targets for T2DM. Sirtuin 1 (SIRT1), a NAD+-dependent histone deacetylase that is induced by CR, is closely associated with lifespan elongation under CR. SIRT1 regulates glucose/lipid metabolism through its deacetylase activity on many substrates. SIRT1 in pancreatic beta-cells positively regulates insulin secretion and protects cells from oxidative stress and inflammation, and has positive roles in the metabolic pathway via the modulation in insulin signaling. SIRT1 also regulates adiponectin secretion, inflammation, glucose production, oxidative stress, mitochondrial function, and circadian rhythms. Several SIRT1 activators, including resveratrol have been demonstrated to have beneficial effects on glucose homeostasis and insulin sensitivity in animal models of insulin resistance. Therefore, SIRT1 may be a novel therapeutic target for the prevention of T2DM, implicating with CR. In this review, we summarize current understanding of the biological functions of SIRT1 and discuss its potential as a promising therapeutic target for T2DM.

Keyword

Caloric restriction; Diabetes mellitus, type 2; Resveratrol; SIRT1

MeSH Terms

Adiponectin
Aging
Caloric Restriction
Circadian Rhythm
Diabetes Mellitus, Type 2
Glucose
Histone Deacetylases
Homeostasis
Inflammation
Insulin
Insulin Resistance
Metabolic Networks and Pathways
Models, Animal
Oxidative Stress
Prevalence
Sirtuin 1
Stilbenes
Adiponectin
Glucose
Histone Deacetylases
Insulin
Sirtuin 1
Stilbenes

Figure

• 

  Fig. 1 Enzymatic activities of sirtuin 1 (SIRT1). NAD+ is consumed as a substrate for the deacetylation of target proteins. The acetyl-lysine residues of the target protein serve as substrates for SIRT1 deacetylation, which generate nicotinamide and 2'-O-acetyl-ADP-ribose (2'-OAADPr) as by products. Nicotinamide acts as a negative feedback inhibitor of SIRT1.

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