title: Islet cannabinoid receptors: cellular distribution and biological function.
abstract: OBJECTIVE
  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 α 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.
authors.affiliation: From the *CENEXA - Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA, Centro Colaborador OPS/OMS para Diabetes), Facultad de Ciencias Médicas, UNLP, La Plata; and †Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Buenos Aires, Argentina.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Flores
authors.forename: María E
authors.initials: ME
authors.lastname: Alzugaray
authors.forename: Marisa A
authors.initials: MA
authors.lastname: Cubilla
authors.forename: María A
authors.initials: MA
authors.lastname: Raschia
authors.forename: Héctor H
authors.initials: HH
authors.lastname: Del Zotto
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Román
authors.forename: Angela M
authors.initials: AM
authors.lastname: Suburo
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D015870:Gene Expression; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D014018:Tissue Distribution
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D005947:Glucose; D000077285:Rimonabant