title: Rosiglitazone inhibits early stage of glucolipotoxicity-induced beta-cell apoptosis.
abstract: OBJECTIVE
  We investigated whether rosiglitazone protects beta-cells from glucolipotoxicity directly.
  
  
  METHODS
  INS-1 cells were incubated with 25 mM glucose and 0.5 mM palmitate in the absence or presence of 2.5 microM rosiglitazone. We evaluated caspase-3 expression and nuclear DAPI staining. An in vivo study was performed, in which 18-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with rosiglitazone (4 mg/kg/day, n = 6) and with placebo (n = 6) for 10 weeks. At 28 weeks of age, an oral glucose tolerance test, insulin sensitivity test, TUNEL assay and histologic examination were performed.
  
  
  RESULTS
  Rosiglitazone attenuated glucolipotoxicity-induced nuclear change and caspase-3 expression for 8 h after treatment, but this effect was not observed at 12 h in INS-1 cells. Rosiglitazone treatment decreased beta-cell apoptosis, preserved beta-cell mass and improved glucose tolerance in OLETF rats.
  
  
  CONCLUSIONS
  The present in vitro findings suggest that rosiglitazone can inhibit the early stage of glucolipotoxicity-induced beta-cell apoptosis. Our results suggest that the antidiabetic action of rosiglitazone is, at least in part, related to a direct effect on beta-cells rather than simply an indirect effect of improving insulin sensitivity.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.forename: Kyu Yeon
authors.initials: KY
authors.lastname: Hur
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: So Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Ahn
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Cha
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004249:DNA Damage; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010168:Palmitates / Q000494:pharmacology; D051381:Rats; D020334:Rats, Inbred OLETF; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D010168:Palmitates; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D002784:Cholesterol; D053148:Caspase 3; D005947:Glucose