Regulation of glucose uptake and differentiation by α-lipoic acid in 3T3-L1 adipocytes = 지방 세포에서 알파 리포산에 의한 당 흡수 및 분화 조절 기작

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$\alpha$-Lipoic acid is known to increase insulin sensitivity in vivo and to stimulate glucose uptake into adipose and muscle cells in vitro. To elucidate the mechanism of this effect, the role of protein thiol groups and $H_2O_2$ production was investigated in α-lipoic acid-stimulated insulin receptor autophosphorylation and glucose uptake into 3T3-L1 adipocytes. α-Lipoic acid or insulin treatment of adipocytes increased intracellular level of oxidants, decreased thiol reactivity of the insulin receptor β-subunit, increased tyrosine phosphorylation of the insulin receptor, and enhanced glucose uptake. α-Lipoic acid or insulin-stimulated glucose uptake was inhibited i) by alkylation of intracellular, but not extracellular, thiol groups downstream to insulin receptor activation, and ii) by diphenylene iodonium at the level of the insulin receptor autophosphorylation. α-Lipoic acid also inhibited protein tyrosine phosphatase activity and decreased thiol reactivity of protein tyrosine phosphatase 1B. These findings indicate that oxidants produced by α-lipoic acid or insulin treatment are involved in activation of IR and in inactivation of protein tyrosine phosphatases, which eventually result in elevated glucose uptake into 3T3-L1 adipocytes. Obesity is closely associated with a number of pathological disorders, including non-insulin-dependent diabetes, hypertension, hyperlipidemia, and cardiovascular diseases. With regard to this wide range of health implications, the need to develop new and effective strategies in controlling obesity has become more acute. However, little is known about the regulation of adipogenesis by $\alpha$-lipoic acid. Here, we demonstrated that co-treatment or post-treatment of 3T3-L1 cells with $\alpha$-lipoic acid down-regulated adipogenesis caused by a cocktail of differentiation inducers and troglitazone. Northern blot and electrophoretic mobility shift assay showed that $\alpha$-lipoic acid regulation of adipogenesis was caused by ...
Advisors
Chung, An-Sik정안식
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
2003
Identifier
180982/325007 / 000985361
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생물과학과, 2003.2, [ xiii, 116 p. ]

Keywords

differentiation; glucose uptake; adipocyte; alpha-lipoic acid; insulin; 인슐린; 분화; 당 흡수; 지방 세포; 알파 리포산

URI
http://hdl.handle.net/10203/27535
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=180982&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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