Grapefruit juice improves glucose intolerance in streptozotocin-induced diabetes by suppressing hepatic gluconeogenesis.

Purpose: Hypoglycemic effects of grapefruit juice (GFJ) are widely recognized, but the mechanism(s) by which GFJ lowers blood glucose levels have not previously been investigated.

Methods: Wistar rats [250-300 g body weight (BW)] were divided into eight groups (n = 7). Group 1 animals were orally treated with 3.0 ml/kg BW of distilled water for 60 days, while groups 3, 4, 5, 6 were similarly treated with 3.0 ml/kg BW of GFJ. Groups 4 and 7 as well as 2, 5, 6 and 8 were given 45.0 and 60.0 mg/kg BW intraperitoneal injections streptozotocin, respectively, while groups 2 and 6 animals were additionally injected with insulin (4.0 units/kg, S.C., b.d), respectively. Fasting blood glucose (FBG) and glucose tolerance tests were done. Hepatic glycogen content and glucokinase, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were measured in homogenized liver tissues.

Results: Diabetic rats, groups 2 and 4-8 exhibited significantly reduced weight gain but increased polydipsia compared to controls. FBG was significantly increased in diabetic rats compared to controls but were significantly improved in GFJ-treated-compared to non-treated-diabetic rats. Similarly, diabetic rats showed significant glucose intolerance compared to controls which was improved by GFJ treatment. GFJ treatment did not improve fasting plasma insulin in diabetic rats. GFJ treatment significantly elevated glucokinase activity and hepatic glycogen concentrations but suppressed the activities of G6Pase and PEPCK, respectively, in diabetic animals.

Conclusion: These findings show that GFJ is not insulinotropic but improves glucose intolerance in diabetic rats by suppressing hepatic gluconeogenesis.