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

Authors
 Seung Jin Han  ;  Eun Seok Kang  ;  Kyu Yeon Hur  ;  Hae Jin Kim  ;  So Hun Kim  ;  Chae-Ok Yun  ;  Sung-E Choi  ;  Chul Woo Ahn  ;  Bong Soo Cha  ;  Yup Kang  ;  Hyun Chul Lee 
Citation
 Hormone Research, Vol.70(3) : 165-173, 2008 
Journal Title
 Hormone Research 
ISSN
 0301-0163 
Issue Date
2008
MeSH
Animals ; Apoptosis/drug effects* ; Caspase 3/biosynthesis ; Cell Line ; Cell Survival/drug effects ; Cholesterol/blood ; DNA Damage ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/pathology* ; Fatty Acids, Nonesterified/blood ; Glucose/pharmacology ; Glucose Tolerance Test ; Hypoglycemic Agents/pharmacology* ; Immunoblotting ; In Situ Nick-End Labeling ; Insulin/blood ; Insulin-Secreting Cells/drug effects* ; Insulin-Secreting Cells/pathology ; Male ; Palmitates/pharmacology ; Rats ; Rats, Inbred OLETF ; Thiazolidinediones/pharmacology* ; Triglycerides/blood
Keywords
Glucolipotoxicity ; Rosiglitazone ; Apoptosis ; Diabetes mellitus
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.
Full Text
http://www.karger.com/Article/FullText/137662
DOI
10.1159/000137662
Appears in Collections:
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Eun Seok(강은석) ORCID logo https://orcid.org/0000-0002-0364-4675
Kim, So Hun(김소헌)
Ahn, Chul Woo(안철우) ORCID logo https://orcid.org/0000-0003-3733-7486
Yun, Chae Ok(윤채옥)
Lee, Hyun Chul(이현철)
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
Han, Seung Jin(한승진)
Hur, Kyu Yeon(허규연)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106736
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