Cannabidiol oil delays pancreatic islet dysfunction in Wistar rats under hypercaloric diet

Abstract

Hypercaloric diet (HCD) intake can lead to metabolic alterations, such as metabolic syndrome and type-2 diabetes mellitus. Phytocannabinoid cannabidiol (CBD) is a GPR55 receptor antagonist involved in insulin secretion and other functions in pancreatic islet. The therapeutic use of CBD has been suggested for diabetes, but little is known regarding its effects on pancreatic islet physiology. Our aim was to evaluate the effects of CBD oil on pancreatic islets, from Wistar rats under HCD. Male rats were divided in 4 groups: Normal diet vehicle-treated (control) and CBD-treated group. Rats under HCD were subdivided in treated with vehicle (HCD) and with CBD oil administered 21 mg/Kg orally, 0.5 ml in 3 days per week; controls received coconut oil as vehicle. Body weight, food intake, and water consumption were recorded. After 20 weeks, glucose tolerance curve was performed; serum insulin was determined by ELISA, and pancreas was removed for histological and gene expression analysis for insulin, glucagon, PDX-1, MafA and GPR55 receptor. CBD treatment reduced body weight and food intake but increased fluid consumption, independently of diets. In control group, CBD did not alter blood glucose and serum insulin, but modified expression for GPR55 receptor, glucagon, insulin and MafA. Rats under HCD and treated with CBD decreased glycaemia, insulinaemia, islets relative area, GPR55-positive cells, PDX-1 and MafA gene expression, meanwhile insulin and glucagon expression was increased. In conclusion, CBD ameliorated HCD effects through changes in insulin, glucagon and GPR55 receptor expressions. We assume CBD interacts with other receptors beside GPR55.