Document Detail


Rosiglitazone inhibits early stage of glucolipotoxicity-induced beta-cell apoptosis.
MedLine Citation:
PMID:  18663317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-29
Journal Detail:
Title:  Hormone research     Volume:  70     ISSN:  1423-0046     ISO Abbreviation:  Horm. Res.     Publication Date:  2008  
Date Detail:
Created Date:  2008-09-03     Completed Date:  2008-11-14     Revised Date:  2008-12-19    
Medline Journal Info:
Nlm Unique ID:  0366126     Medline TA:  Horm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  165-73     Citation Subset:  IM    
Copyright Information:
Copyright 2008 S. Karger AG, Basel.
Affiliation:
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Caspase 3 / biosynthesis
Cell Line
Cell Survival / drug effects
Cholesterol / blood
DNA Damage
Diabetes Mellitus, Type 2 / blood,  drug therapy,  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*,  pathology
Male
Palmitates / pharmacology
Rats
Rats, Inbred OLETF
Thiazolidinediones / pharmacology*
Triglycerides / blood
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Palmitates; 0/Thiazolidinediones; 0/Triglycerides; 11061-68-0/Insulin; 122320-73-4/rosiglitazone; 50-99-7/Glucose; 57-88-5/Cholesterol; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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