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KMID : 0613820070170010056
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Journal of Life Science
2007 Volume.17 No. 1 p.56 ~ p.63
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Molecular Events of Insulin Action Occur at Lipid Raft/Caveolae in Adipocytes
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Bae Sun-Sik
Yun Sung-Ji
Kim Eun-Kyung
Kim Chi-Dae
Choi Jang-Hyun
Suh Pan-Ghil
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Abstract
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Insulin stimulates the fusion of intracellular vesicles containing glucose transporter 4 (GLUT4) with plasma membrane in adipocytes and muscle cells. Here we show that adipocyte differentiation results in enhanced insulin sensitivity of glucose uptake. On the other hand, glucose uptake in response to platelet-derived growth factor (PDGF) stimulation was markedly reduced by adipocyte differentiation. Expression level of insulin receptor and caveolin-1 was dramatically increased during adipocyte differentiation. Adipocyte differentiation caused slightly enhanced activation of acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) by insulin stimulation. However, activation of Akt by PDGF stimulation was largely reduced. Activation of ERK was not detected in both fibroblasts and adipocytes after stimulation with insulin. PDGF-dependent activation of ERK was reduced by adipocyte differentiation. Insulin-dependent glucose uptake was abrogated by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, in both fibroblasts and adipocytes. Also disassembly of caveolae structure by methyl-β-cyclodextrin caused impairment of Akt activation and glucose uptake. Finally, insulin receptor, Akt, SH2-domain-containing inositol 5-phosphatase 2 (SHIP2), and regulatory subunit of PI3K are localized at lipid raft domain and the translocation was facilitated upon insulin stimulation. Given these results, we suggest that lipid raft provide proper site for insulin action for glucose uptake.
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KEYWORD
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glucose uptake, GLUT4, Akt, Insulin, lipid raft
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