Effects of cannabinoid–1 receptor on pancreatic beta–cell function in obese rats

Abstract

Objective To investigate the effects of cannabinoind–1 receptor (CB1R) on pancreatic beta–cell function in obese rats. Methods A total of 30 male 8–week healthy SD rats were randomly assigned to the control group (n=6) or obesity group (n=24). After 8 weeks' intervention, 24 obese rats were randomly divided into the saline group (n=8), WIN55212–2 injection group (n=8) and AM251 injection group (n=8). The body weight, insulin, lipids, and proinsulin levels were measured in fasting status. Hyperglycemic clamp was performed to evaluate the insulin sensitivity and islet beta–cell function. LSD test was used for data analysis. Results After 2–week peritoneal injection, compared with the control group, body weight, lipids, fasting glucose, C peptide, insulin, proinsulin, proinsulin/C peptide, proinsulin/insulin, 10 to 90 min insulin release and maximum insulin secretion were significantly higher in the saline or WIN55212–2 injection group (all P<0.05). These parameters in the WIN55212–2 injection group were higher than those in the saline group (all P<0.05). Above measurements in the AM251 injection group were lower than those in the saline or WIN55212–2 injection group (all P<0.05). Compared with the control group, 0 to 10 min insulin release and glucose infusion rate (GIR) were significantly lower in the saline or WIN55212–2 injection group (all P<0.05). GIR and 0 to 10 min insulin release in the WIN55212–2 injection group were lower than those in the saline group. GIR and 0 to 10 min insulin release in the AM251 injection group were higher than those in the saline or WIN55212–2 injection group. Conclusion Agitating CB1R could elevate body weight, lipid profile, insulin resistance and islet beta–cell function impairment in obese rats. Restraining CB1R could reverse those effectiveness. Key words: Cannabinoid–1 receptors; Islet beta–cell function; Insulin resistance; Obese rats