Justyna Strycharz, Zaneta Rygielska, Ewa Swiderska, Jozef Drzewoski, Janusz Szemraj, Leszek Szmigiero and Agnieszka Sliwinska* Pages 1002 - 1035 ( 34 )
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.
SIRT1, insulin resistance, diabetes, diabetic complications, SIRT1-associated epigenetics, SIRT1- targeting drugs.
Department of Medical Biochemistry, Medical University of Lodz, Lodz, Diabetes Student Scientific Society at the Department of Internal Disease, Diabetology and Clinical Pharmacology, Medical University of Lodz, Lodz, Department of Medical Biochemistry, Medical University of Lodz, Lodz, Central Teaching Hospital of the Medical University of Lodz, Lodz, Department of Medical Biochemistry, Medical University of Lodz, Lodz, Department of Nucleic Acids Biochemistry, Medical University of Lodz, Lodz, Department of Nucleic Acids Biochemistry, Medical University of Lodz, Lodz