Suppression of phosphoenolpyruvate carboxykinase gene expression by secoisolariciresinol diglucoside (SDG), a new antidiabetic agent

Abstract

Secoisolariciresinol diglucoside (SDG) from flaxseed has been shown to be effective in preventing/delaying the development of type-1 and type-2 diabetes. The hypoglycemic effect of SDG in type-2 diabetes has been suggested to be due to its antioxidant activity. Hyperglycemia in type-2 diabetes could be due to an increase in the expression of phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in the gluconeogenesis in the liver. It is possible that the hypoglycemic effect of SDG in type-2 diabetes is due to suppression of expression of PEPCK gene. An investigation, therefore, was made on the effect of SDG on the PEPCK gene expression. Primary hepatocyte culture was treated with insulin, a physiological inhibitor of PEPCK gene expression, or with SDG for 12 hours. After RNA extractions, Northern blot analysis was done. SDG in the concentration of 100 μM completely suppressed the expression of PEPCK gene. Insulin in the concentration of 10 nM almost completely suppressed the PEPCK gene expression. The results suggest that SDG suppresses the expression of PEPCK gene and that its known hypoglycemic effect may be due to suppression of PEPCK gene expression.