Original Paper

Rosiglitazone Inhibits Early Stage of Glucolipotoxicity-Induced Beta-Cell Apoptosis
Seung Jin Han^a, Eun Seok Kang^a-c, Kyu Yeon Hur^a, Hae Jin Kim^e, So Hun Kim^a, Chae-Ok Yun^d, Sung-E Choi^f, Chul Woo Ahn^a-c, Bong Soo Cha^a-c, Yup Kang^f, Hyun Chul Lee<sup>a-c

a</sup>Department of Internal Medicine,
^bBrain Korea 21 for Medical Science, and
^cInstitute of Endocrine Research, Yonsei University College of Medicine,
^dInstitute for Cancer Research, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul,
^eDepartment of Endocrinology, Ajou University School of Medicine,
^fLaboratory of Endocrinology, Institute for Medical Science, Ajou University School of Medicine, Suwon, South Korea

Address of Corresponding Author

Horm Res 2008;70:165-173 (DOI: 10.1159/000137662)

  Key Words

• Glucolipotoxicity
• Rosiglitazone
• Apoptosis
• Diabetes mellitus

  Abstract

Aim: We investigated whether rosiglitazone protects -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 µM 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 -cell apoptosis, preserved -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 -cell apoptosis. Our results suggest that the antidiabetic action of rosiglitazone is, at least in part, related to a direct effect on -cells rather than simply an indirect effect of improving insulin sensitivity.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Hyun Chul Lee, MD, PhD
Division of Endocrinology and Metabolism
Department of Internal Medicine, Yonsei University College of Medicine
134 Shinchon-dong, Seodaemun-gu, Seoul (South Korea)
Tel. +82 2 2228 1943, Fax +82 2 393 6884, E-Mail endohclee@yumc.yonsei.ac.kr

  Article Information

Eun Seok Kang and Seung Jin Han contributed equally to this work.

Received: March 19, 2007
Accepted: October 25, 2007
Published online: July 29, 2008
Number of Print Pages : 9
Number of Figures : 7, Number of Tables : 1, Number of References : 30