Title:SIRT1 as a Therapeutic Target in Diabetic Complications
Volume: 25
Issue: 9
Author(s): Justyna Strycharz, Zaneta Rygielska, Ewa Swiderska, Jozef Drzewoski, Janusz Szemraj, Leszek Szmigiero and Agnieszka Sliwinska*
Affiliation:
- Department of Nucleic Acids Biochemistry, Medical University of Lodz, Lodz,Poland
Keywords:
SIRT1, insulin resistance, diabetes, diabetic complications, SIRT1-associated epigenetics, SIRT1-
targeting drugs.
Abstract: Background: Sirtuin1 is an epigenetic enzyme involved in histone and nonhistone
protein deacetylation. It acts primarily as a metabolic sensor, which responses to
changing energy status by deacetylating crucial transcription factors and cofactors. In this
way, Sirtuin1 regulates mitochondrial function and biogenesis, oxidative stress, inflammation,
apoptosis and cellular senescence. Disturbance of all of these phenomena promotes
the pathogenesis of diabetic complications. These disorders are inseparably connected
with chronic hyperglycemia, which possesses a strong epigenetic determinant.
Objective: To summarize the contemporary knowledge regarding the role of Sirtuin1 in
the development, progression and therapy of diabetic complications.
Methods: We extensively searched literature describing the importance of Sirtuin1 in
pathophysiology and treatment of all kinds of diabetic complications till September 2017.
We focused on the examples of synthetic and natural compounds-mediated Sirtuin1 upregulation
along with Sirtuin1-associated epigenetics.
Results: Reduction of Sirtuin1 is implicated in endothelial dysfunction and metabolic
memory, underlying the development of micro- and macrovascular complications. Declined
Sirtuin1 also participates in diabetic testicular and erectile dysfunction. Sirtuin1 is
elevated by naturally occurring anti-oxidant and anti-inflammatory compounds such as
resveratrol, trans-δ-viniferin, vitamin D and more. Similarly, Sirtuin1 level increases after
treatment with standard antihyperglycemic (metformin, exenatide, liraglutide), antihypertensive
(sartans), lipid-lowering (fibrates, statins) and anticoagulant (fidarestat) drugs.
Regarding epigenetics, a number of miRNAs trigger Sirtuin1 decrease, which further contributes
to histone acetylation of Sirtuin1-regulated and relevant for diabetes genes.
Conclusion: Evidence strongly suggest that Sirtuin1 upregulation may serve as a potent
therapeutic approach against development and progression of diabetic complications.
