Effect of Thymoquinone on Insulin Sensitivity in STZ- Nicotinamide Type 2 Diabetic Rats

Abstract

This is an analytical case control study conducted to investigate the effect of thymoquinone on insulin sensitivity in STZ- Nicotinamide type 2 diabetic rats. The experimental animals were fifty adult male Wistar rats. Diabetes was induced in 44 rats by intraperitoneal injection (i.p) of sterptozotocin (STZ) 15 minutes after administration of Nicotinamide (NA). The rest of the rats (six) received only a vehicle (olive oil) were considered the nondiabetic control group (NNG). Fasting blood glucose (FBG) level was measured at 72 hours following induction of diabetes. Rats with FBG ≥250mg/dl were considered diabetic. Then the diabetic rats were randomly divided into six groups four of them were treated with different doses of Thymoquinone (TQ) (TQ10, TQ30, TQ60 and TQ80 receiving 10, 30, 60, 80 mg/kg B.W. respectively), the fifth group was treated with metformin 120mg/kgB.W (MET) and the sixth group was not given any treatment except a vehicle (olive oil) and was considered as the negative diabetic control group (NDG). All rats were weighed at day zero and at the end of the experiment. Eight weeks after treatment oral glucose tolerance test (OGTT) was performed and blood samples were taken for measuring the lipid profile, urea, creatinine and hepatic enzymes. Samples from the liver were taken for histopathological examination and from the skeletal muscles for measuring insulin receptors (IR) by ELISA and quantitative real time PCR (qRT-PCR). TQ60, TQ80 and (NNG) showed a significant increase in body weight (P value = 0.001, 0.01 and 0.03 respectively). FBG of TQ30, TQ60, TQ80 and MET was significantly reduced after the treatment (P value = 0.002, 0.05, 0.013 and 0.005 respectively). OGTT was improved by the highest dose TQ80. High-density lipoprotein cholesterol (HDL-c) was significantly low in TQ10, TQ30 and NDG (P value = 0.000, 0,018 and 0.006 respectively) when compared with NNG while it was significantly high in TQ60mg and TQ80mg when compared with NDG (P values were 0.000 and 0.019 respectively). Blood urea and creatinine, hepatic enzymes, low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) were within the normal range. Significant hepatic histopathological changes were found in NDG compared with the treated groups. IR was reduced in all diabetic groups compared with NNG (P value = 0.000). Expression of IR was significantly increased in TQ10 (P value = 0.013 and 0.003 when compared with NNG and MET respectively). It was concluded that TQ is safe to use up to a dose level of 80 mg/kg B.W with effective hypoglycemic activity.