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Rosiglitazone inhibits early stage of glucolipotoxicity-induced beta-cell apoptosis.

Authors
Han, SJ; Kang, ES; Hur, KY; Kim, HJ; Kim, SH; Yun, CO; Choi, SE; Ahn, CW; Cha, BS; Kang, Y; Lee, HC
Citation
Hormone research, 70(3):165-173, 2008
Journal Title
Hormone research
ISSN
0301-01631423-0046
Abstract
AIM: 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. CONCLUSION: 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.
MeSH terms
AnimalsApoptosis/drug effects*Caspase 3/biosynthesisCell LineCell Survival/drug effectsCholesterol/bloodDNA DamageDiabetes Mellitus, Type 2/bloodDiabetes Mellitus, Type 2/drug therapyDiabetes Mellitus, Type 2/pathology*Fatty Acids, Nonesterified/bloodGlucose/pharmacologyGlucose Tolerance TestHypoglycemic Agents/pharmacology*ImmunoblottingIn Situ Nick-End LabelingInsulin/bloodInsulin-Secreting Cells/drug effects*Insulin-Secreting Cells/pathologyMalePalmitates/pharmacologyRatsRats, Inbred OLETFThiazolidinediones/pharmacology*Triglycerides/blood
DOI
10.1159/000137662
PMID
18663317
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
한승진김혜진최성이강엽
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