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Journal of Biochemistry Advance Access published online on October 26, 2007
Journal of Biochemistry, doi:10.1093/jb/mvm172
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© 2007 The Japanese Biochemical Society

Gliclazide inhibits proliferation but stimulates differentiation of white and brown adipocytes.

Norihiko Nakanoa,#, Nobuko Miyazawaa, Takuya Sakuraia, Takako Kizakia, Kiyoko Kimotoa, Kazuto Takahashib, Hitoshi Ishidab, Motoko Takahashic, Kenji Suzukid and Hideki Ohnoa

a Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
b Third Department of Internal Medicine, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
c Department of Biochemistry, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan
d Laboratory of Molecular Medicinal Sciences, Department of Bioscience and Bioinformatics, College of Information Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan

#To whom correspondence should be addressed: Dr. Nakano Norihiko, Aino Institute of Regeneration and Rehabilitation, 4-5-11 Higashiohda, Ibaraki, Osaka 567-0012, Japan. Tel: +81-72-621-5087, FAX: +81-72-627-7882, E mail: n-nakano{at}aino.ac.jp (present address)

Received July 8, 2007; Accepted August 30, 2007


  Abstract

Gliclazide, a second-generation sulfonylurea, has anti-oxidant properties as well as hypoglycemic activities. In the present study, we investigated whether gliclazide affected proliferation and/or differentiation of HW white and HB2 brown adipocyte cell lines. Gliclazide inhibited proliferation of HW and HB2 cells in the medium containing fetal calf serum or epidermal growth factor (EGF). Gliclazide inhibited phosphorylation of EGF receptor and of extracellular signal-regulated kinase (ERK) 1/2 stimulated by EGF. Gliclazide increased lipid accumulation and peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) expression in the early stage of differentiation of adipocytes. A KATP channel activator, diazoxide, did not inhibit the increase of lipid accumulation by gliclazide. Futhermore, gliclazide inhibited the DNA-binding activity of PPAR-{gamma} in mature adipocytes. On the other hand, glibenclamide, other sulfonylurea, did not show these effects. These results indicate gliclazide inhibits proliferation and stimulates differentiation of adipocytes via downregulation of the EGFR signaling. Gliclazide may have preventive and therapeutic effects on obesity, as well as type 2 diabetes.

Key Words: adipocyte, EGF, gliclazide, PPAR{gamma}, proliferation & differentiation


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