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Background  Tomato fruit ( Lycopersicon esculentum  Mill.) has been suggested to be useful for the prevention of diabetes. Esculeoside A is the main saponin compounds in tomatoes. This study investigated the hypoglycemic effects and the underlying mechanism of esculeoside A in C57BLKS/Leprdb ( db/db ) mice.    Methods  Wild-type C57BLKS ( db/dm ) mice were used in the  db/dm  mouse group and  db/db  mice were randomly divided into 2 groups: untreated and treated  db/db  mouse groups. Esculeoside A (100 mg/kg) was administered by gavage for 56 days to the treated  db/db  mouse group. Distilled water was administered to the  db/dm  mouse group and the untreated  db/db  mouse group. The blood and liver biochemical parameters and the expression of liver insulin signaling-related proteins were examined.    Results  The results showed that esculeoside A reduced the fasting blood glucose (FBG) levels and improved the glucose tolerance. Further investigation revealed that hepatic protein expressions of total AMP-activated protein kinase (T-AMPK), phosphorylated AMP-activated protein kinase (p-AMPK), insulin receptor substrate-1 (IRS-1), and glucokinase (GCK) were significantly upregulated after esculeoside A treatment. In contrast, the hepatic protein expression of phosphoenolpyruvate carboxykinase (PEPCK) was significantly downregulated by esculeoside A treatment.    Conclusion  These findings suggested that esculeoside A has a potential of alleviating the metabolic abnormalities in  db/db  mice via regulation of AMPK/IRS-1 pathway. Our findings supported a possible application of esculeoside A as a functional supplement for diabetes treatment.

Hypoglycemic effects of esculeoside A are mediated via activation of AMPK and upregulation of IRS-1