3-Deazaadenosine,Mechanism Of Action In Liver Glucosemetabolism

S-adenosine homocysteine hydrolase(SAHH)is widely expressed in many tissues including liver.It catalyzes the hydrolysis of s-adenosine homocysteine(SAH)to produce homocysteine(Hcy)and adenosine(Ado),which plays an important role in the homeostasis of methyl cycle in vivo.The liver is the control center of glycolipid metabolism.Abnormal elevated gluconeogenesis and insulin resistance contribute to the progress of type 2 diabetes.Whether SAHH plays a role in hepatic glucose production and insulin sensitivity is not fully understood.In this study,we showed that 3-deazaadenosine(DAA),a specific inhibitor of SAHH,decreases HGP and increases insulin sensitivity in hepatocytes.DAA promotes the phosphorylation of AKT,thus enhancing the sensitivity of liver insulin.At the same time,DAA inhibits hepatic glucose production by suppressing the expression of G6 Pase,PEPCK and CREB.This study indicates that inhibition of SAHH is a novel potential strategy for the treatment of hyperglycemia in obesity and type 2 diabetes.