title: Reduced food intake is the major contributor to the protective effect of rimonabant on islet in established obesity-associated type 2 diabetes.
abstract: OBJECTIVE
  Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake.
  
  
  METHODS
  After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group).
  
  
  RESULTS
  Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p< 0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups.
  
  
  CONCLUSIONS
  Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.
authors.affiliation: Division of Endocrinology and Metabolism, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea.
authors.forename: Sang-Man
authors.initials: SM
authors.lastname: Jin
authors.forename: Bae Jun
authors.initials: BJ
authors.lastname: Oh
authors.forename: Suel
authors.initials: S
authors.lastname: Lee
authors.forename: Jung Mook
authors.initials: JM
authors.lastname: Choi
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Yang
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Kwang-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy*; D004435:Eating / Q000187:drug effects*; D018149:Glucose Intolerance / Q000178:diet therapy / Q000188:drug therapy*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D020334:Rats, Inbred OLETF; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D000077285:Rimonabant; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077285:Rimonabant
keywords: Cannabinoid receptor CB1; islet; rimonabant; type 2 diabetes
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