Diabetes, Metabolic Syndrome and Obesity (Jun 2019)
GLP-1 mediates the modulating effect of thymoquinone on feeding behaviors in diabetic rats
Abstract
Shu Ping Lee,1 Feng Yu Kuo,1,2 Juei-Tang Cheng,3,4 Ming Chang Wu11Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan; 2Cardiovascular Center, Veterans General Hospital, Kaohsiung City 81362, Taiwan; 3Department of Medical Research, Chi-Mei Medical Center, Tainan City 71003, Taiwan; 4Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City 71101, TaiwanBackground: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia.Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9–39 (Ex 9–39) were separately administered to TQ- or vehicle-treated diabetic rats.Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9–39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects.Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.Keywords: thymoquinone, GLP-1, sitagliptin, body weight, food intake
