Sirtuin 6, a possible therapeutic target for type 2 diabetes

• Published in: Archives of pharmacal research Vol. 40; no. 12; pp. 1380 - 1389
• Main Author: Bae, Eun Ju
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.12.2017; 대한약학회
• Subjects: adiposity; animal models; Animals; chromatin; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - enzymology; genomics; gluconeogenesis; glucose tolerance; glucose transporters; glycolysis; homeostasis; Humans; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; insulin secretion; longevity; mammals; Medicine; neoplasms; noninsulin-dependent diabetes mellitus; obesity; pathophysiology; Pharmacology/Toxicology; Pharmacy; Review; Sirtuins - antagonists & inhibitors; Sirtuins - metabolism; skeletal muscle; triacylglycerols; 약학; Sirtuins; Deacetylase; Type 2 diabetes mellitus; Glucose homeostasis; SIRT6 activator; SIRT6 inhibitor
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-017-0989-8

Sirtuin 6 (SIRT6), one of the seven members of mammalian sirtuin family, localizes in the nucleus and primarily regulates chromatin signaling and genomic integrity. Recent studies established the critical role of SIRT6 in the pathophysiology of metabolic disease, as well as its roles in longevity and cancer. These roles that were determined by genetic studies include promoting pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride synthesis, and suppressing adiposity, suggesting that SIRT6 activators are promising molecules for treating obesity and diabetes. 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. This review summarizes the confounding findings on the role of SIRT6 in metabolic homeostasis and discusses the possible relationships of these findings as they relate to the use of SIRT6 as a therapeutic target for type 2 diabetes and related diseases.