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

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 (PPARgamma) expression in the early stage of differentiation of adipocytes. A K(ATP) channel activator, diazoxide, did not inhibit the increase of lipid accumulation by gliclazide. Furthermore, gliclazide inhibited the DNA-binding activity of PPARgamma 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 down-regulation of the EGFR signalling. Gliclazide may have preventive and therapeutic effects on obesity, as well as on type 2 diabetes.

• Authors: Norihiko Nakano, Nobuko Miyazawa, Takuya Sakurai, Takako Kizaki, Kiyoko Kimoto, Kazuto Takahashi, Hitoshi Ishida, Motoko Takahashi, Kenji Suzuki, Hideki Ohno
• Journal: Journal of biochemistry (J Biochem) Vol. 142 Issue 5 Pg. 639-45 (Nov 2007) ISSN: 0021-924X [Print] England
• PMID: 17965069 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• PPAR gamma
• Sulfonylurea Compounds
• Epidermal Growth Factor
• ErbB Receptors
• Extracellular Signal-Regulated MAP Kinases
• Gliclazide
• Diazoxide
• Glyburide

Topics

• Adipocytes, Brown (cytology, drug effects, metabolism)
• Adipocytes, White (cytology, drug effects, metabolism)
• Animals
• Blotting, Western
• Cell Differentiation (drug effects)
• Cell Line
• Cell Proliferation (drug effects)
• Diazoxide (pharmacology)
• Epidermal Growth Factor (antagonists & inhibitors, genetics)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, genetics)
• Gene Expression Regulation (drug effects, physiology)
• Gliclazide (pharmacology)
• Glyburide (pharmacology)
• Hypoglycemic Agents (pharmacology)
• Mice
• PPAR gamma (genetics, metabolism)
• Phosphorylation
• Signal Transduction
• Sulfonylurea Compounds (pharmacology)