Sirt2 facilitates hepatic glucose uptake by deacetylating glucokinase regulatory protein

Diabetes drug target

23 April 2018

A liver enzyme implicated in regulating blood sugar levels could provide a new therapeutic target for preventing type 2 diabetes (T2D) and mitigating its effects.

A team from Japan, led by researchers from Kanazawa University, showed that a protein called Sirt2 — a member of the sirtuin family of enzymes — is needed for the liver to properly remove excess glucose from the bloodstream for energy storage. Sirt2, they found, works by binding and activating another protein called GKRP involved in increasing glucose uptake after eating.

In mouse models of diabetes, experimentally boosting levels of Sirt2 enhanced glucose uptake in the liver moderated the health consequences of impaired glucose tolerance.

A similar therapeutic strategy could help people with high blood sugar and pre-diabetes avoid developing the disease. Augmenting Sirt2 expression pharmacologically in patients with T2D could also lessen the risk of cardiovascular complications associated with abnormal spikes of blood glucose.

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References

1. Nature Communications 9, 30 (2018). doi: 10.1038/s41467-017-02537-6