The effects of naringin on glucose tolerance and ketoacidosis in type 1 diabetes.

Abstract

The effects of naringin (4’,5,7-trihydroxy flavonone-7-rhamnoglucoside), a flavonoid isolated from the grapefruit and other citrus fruit species were investigated on diabetic ketoacidosis (DKA) in a type 1 diabetic rat model. DKA is an acute life threatening complication of diabetes mellitus. Male Sprague-Dawley rats (225-250g) were divided into 5 groups (n=7). Group 1 (control) was treated daily with 1.0 ml/kg distilled water while group 2 was treated with 50 mg/kg of naringin, via gastric gavage respectively. Diabetes was induced in groups 3, 4 and 5 by a single intraperitoneal injection of 60 mg/kg streptozotocin in 0.1 M citrate buffer and was confirmed after 48 hours. Group 3 was further treated with subcutaneous insulin (4 IU/kg) twice daily respectively. Blood samples for analysis were collected by cardiac puncture. The animals were handled humanely according to the guidelines of the Animal Ethics Committee, University of KwaZulu Natal, number 106/13/Animal. The untreated diabetic rats (group 5) showed significant (p<0.0001) hyperglycemia, polydipsia, polyuria, weight loss, impaired glucose tolerance, low fasting plasma insulin (FPI) and low glycogen levels compared to the normal control. They also showed significantly (p<0.0001) elevated acetoacetate (AcAc), β-hydroxybutyrate (3HB), total ketone body (TKB), anion gap (AG) and potassium (p<0.05) levels compared to normal control. Furthermore, significant (p<0.01) reductions blood pH, sodium, chloride and bicarbonate (p<0.0001) levels were recorded compared to the normal control. Treatment of the diabetic groups with naringin did not improve fasting blood glucose and serum electrolyte levels but significantly improved weight loss (p<0.0001), water consumption (p<0.0001), hepatic glycogen level (p<0.05), 3HB (p<0.05), AcAc (p<0.05), TKB (p<0.01), bicarbonate (p<0.01), blood pH (p<0.01) and AG (p<0.05) compared to the diabetic control group. The results in this study therefore suggest that naringin reverses ketoacidosis but does not improve glucose tolerance in a diabetes type 1 rat model.