CB1 cannabinoid receptor expression is regulated by glucose and feeding in rat pancreatic islets

Abstract

Endocannabinoid system is involved in food intake and energy balance. Beside the hypothalamus, pancreatic islet also expresses CB1 cannabinoid receptor, however little is known about its physiological role and regulation. Since gene expression of many specific proteins of the islet depends on the concentration of glucose, we studied CB1 receptor expression in response to fasting and feeding. Whole pancreas or islets were isolated from food-deprived adult Wistar rats, with or without a previous 1.5 g/kg glucose oral-intake. CB1, insulin and glucagon expressions were analyzed by confocal immunofluorescence and PCR. In vitro, rat islets were cultured at different glucose concentrations, in the presence of anandamide, or with Rimonabant analog BAR-1. CB1, insulin, glucagon, glucokinase, and PDX-1 expression were determined by real-time RT-PCR, and insulin secretion and islet content by ELISA. CB1 expression in pancreatic islets is upregulated during food restriction, and decreases in response to glucose intake or feeding. In cultured islets, 16 mmol/l glucose, BAR-1, and anandamide at low glucose reduced CB1 mRNA. Insulin, glucagon, glucokinase and PDX-1 expression increased in islets treated with anandamide at low glucose, while BAR-1 modified PDX-1 and glucagon mRNA at high glucose. Basal insulin secretion and insulin content in islets increased with anandamide, but not the glucose-stimulated response. Our results suggest that the endocannabinoid system has an important role in gene expression on islets and its close relationship with glucose response.