Effect of L-citrulline supplementation on blood glucose level and lipid profile in high-fat diet - and dexamethasone-induced type-2 diabetes in male wistar rats

Background: Diabetes mellitus (DM) is one of the most common metabolic disorders, afflicting over 415 million people worldwide. It has been associated with several complications mainly due to hyperglycemia and dyslipidemia. L-Citrulline, a nonessential amino acid may be an efficient alternative therapy owing to its hypolipidemic and other beneficial effects which have not been extensively explored in type-2 DM (T2DM). Objective: We investigated the effect of L-citrulline supplementation on fasting blood glucose (FBG) level and lipid profile in high-fat-diet (HFD) and dexamethasone-induced T2DM in male Wistar rats. Materials and Methods: Thirty male Wistar rats, 10–12 weeks old, each weighing between 200 and 250 g were randomly assigned into six groups of five rats each. Group I was fed normal diet while diabetes was induced in the other groups with HFD and dexamethasone intraperitoneally (1 mg/kg) for 21 days. Group III which was confirmed diabetic, received metformin 100 mg/kg orally, and Groups IV, V, and VI which were also confirmed diabetic, received 200 mg/kg, 400 mg/kg, and 800 mg/kg L-citrulline, respectively, for 21 days. Serum FBG and lipid profile were obtained after humanely sacrificing the rats at the end of the treatment. Values at P < 0.05 were considered statistically significant. Results: At the end of the treatment, L-citrulline significantly reduced the FBG levels in a dose-dependent manner to 192.5 ± 3.4 mg/dL, 181.8 ± 1.2 mg/dL, and 174.8 ± 2.8 mg/dL at 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The total cholesterol level was significantly lowered by L-citrulline 200 mg/kg (55.2 ± 0.64 mg/dL), 400 mg/kg (57.8 ± 1.19 mg/dL), and 800 mg/kg (63.1 ± 1.50 mg/dL) compared to the diabetic control (149.8 ± 2.68 mg/dL). Similar findings were obtained for the low-density lipoprotein and triglyceride levels. There were also significant elevations in the high-density lipoprotein levels by L-citrulline at all doses compared to diabetic control (24.6 ± 1.1 mg/dL). Conclusion: L-Citrulline supplementation possesses antihyperglycemic and antidyslipidemic effects in diabetic Wistar rats.