Islet Cannabinoid Receptors: Cellular Distribution and Biological Function

Objectives This study aimed 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 retrotranscription–polymerase chain reaction) 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 on serum glucose, triglyceride, and insulin levels; homeostasis model assessment for insulin resistance, GSIS, and CBs and insulin receptor substrate gene expression levels (real-time polymerase chain reaction). Results Cannabinoid receptors appeared exclusively in islet &agr; cells. Whereas different CB agonists enhanced GSIS in normal rat islets, R did not affect it. F rats had higher serum triglyceride and insulin levels and homeostasis model assessment for insulin resistance 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 insulin receptor substrate gene expression. Conclusions Islet CBs would exert an important modulatory role in metabolic homeostasis. Administration of R and F affected islet CB expression and prevented the development of F-induced metabolic impairment. Selective islet CB1 blockers could be useful to prevent/treat the alterations induced by the intake of unbalanced/unhealthy diets.

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