Islet Cannabinoid Receptors Cellular Distribution and Biological Function

Abstract

Objectives: To determine the cellular distribution of islet cannabinoid receptors (CBs) and their involvement in the development of metabolic and hormonal changes in rats fed a fructose-rich diet (F). Methods: In normal rat islets, we determined CBs (immunofluorescence and RT-PCR) and glucose-stimulated insulin secretion (GSIS) of isolated islets incubated with the CB1 antagonist rimonabant (R) and/or different CBs agonists. In 3-week F-fed rats, we determined the in vivo effect of R upon serum glucose, triglyceride and insulin levels, HOMA-IR, GSIS and CBs and IRS gene expression levels (real-time PCR). Results: CBs appeared exclusively in islet α-cells. Whereas different CBs agonists enhanced GSIS in normal rat islets, R did not affect it. F rats had higher serum triglyceride and insulin levels and HOMA-IR than control rats; these alterations were prevented by R coadministration. Although R did not correct the increased GSIS observed in F islets, it modulated CBs and IRS gene expression. Conclusion: Islet CBs would exert an important modulatory role in metabolic homeostasis. Administration of R and F affected islet CBs expression and prevented the development of Finduced metabolic impairment. Selective islet CB1 blockers could be useful to prevent/treat the alterations induced by the intake of unbalanced/unhealthy diets.