胰島素、第一型及第二型類胰島素生長因子、表沒食子酸酯型唲茶素酸酯（英文名epigallocatechin gallate；簡稱EGCG）都已被證實會調節脂肪細胞的功能。但是，關於EGCG對胰島素和類胰島素生長因子刺激前脂肪細胞增生和脂肪細胞的葡萄糖攝取之影響，其作用機制上仍不明瞭。在論文第一章中，我們發現EGCG使胰島素所促進信息蛋白的磷酸化受到抑制，如胰島素接受器(IR)、IRS1、IRS2、RAF1、MEK1/2、ERK1/2的磷酸化受到抑制，但JNK的磷酸化未受影響。EGCG抑制IR與IRS1和IRS2兩者之間的結合作用，但與IRS4結合未受影響。這些研究顯示，EGCG的選擇性影響特定類型的IRS和MAPK蛋白。EGCG使胰島素所促進67LR和IR、IRS1、IRS2、IRS4蛋白結合作用增加。這些研究顯示，EGCG抑制胰島素訊息而使前脂肪細胞增生受到抑制是經由67LR的訊息傳導。在第二章中，我們發現EGCG抑制IGF-Ⅰ和IGF-Ⅱ所刺激的p66Shc和MAPK訊息分子的磷酸化，包括RAF1、MEK1、ERK1/2蛋白質的磷酸化，但PKB、p52Shc、或p46Shc不受影響 。此外，我們的研究顯示，EGCG抑制第一型及第二型類胰島素生長因子訊息而使前脂肪細胞增生受到抑制是經由67LR途徑而不是AMPK的途徑。在第三章中，我們發現EGCG抑制IGF-I和IGF-Ⅱ所刺激脂肪細胞的葡萄糖攝取是經由67LR路徑。EGCG抑制IGF-I和IGF-Ⅱ所刺激之PKCζ/λ磷酸化，但ERK和AKT的磷酸化未受抑制。在3T3-L1脂肪細胞，EGCG抑制IGF-I和IGF-Ⅱ刺激葡萄糖攝取是藉由減少GLUT4轉位(translocation)和67LR和AMPK途徑。此論文研究結果有助於說明EGCG調節胰島素、IGF-Ⅰ、IGF-Ⅱ於脂肪細胞的作用機制，以及EGCG調節體重的作用機制。

Insulin, insulin-like growth factor (IGF)-I and -II, and (−)-epigallocatechin gallate (EGCG) have been reported to regulate fat cell functions. However, it is still not clear how EGCG acts on insulin and IGFs signaling pathways for stimulating mitogenesis and glucose uptake in fat cells. The first chapter indicated that EGCG suppressed insulin-stimulated phosphorylation of the insulin receptor-β, insulin receptor (IR) substrates 1 and 2 (IRS1 and IRS2), and MAPK pathway proteins, RAF1, MEK1/2, and ERK1/2, but not JNK. EGCG inhibited the association of IR with the IRS1 and IRS2 proteins, but not with the IRS4 protein. These data suggest that EGCG selectively affects particular types of IRS and MAPK family members. EGCG tended to increase insulin-stimulated associations between the 67LR and IR, IRS1, IRS2, and IRS4 proteins. These data suggest that EGCG mediates anti-insulin signaling in preadipocyte mitogenesis via the 67LR pathway. The second chapter indicated that EGCG suppressed IGF-I-stimulated and IGF-II-stimulated phosphorylation of p66Shc and MAPK pathway proteins, including RAF1, MEK1, and ERK1/2, but not JNK, protein kinase B, p52Shc, or p46Shc. Furthermore, we demonstrated that EGCG mediates anti-IGF-I and anti-IGF-II signals in preadipocyte mitogenesis via the 67LR but not the AMPK pathway. The third chapter indicated that EGCG inhibited IGF-I and IGF-II stimulation of adipocyte glucose uptake. The 67LR mediated the effect of EGCG on IGF-stimulated glucose uptake in adipocytes. EGCG suppressed the IGF-stimulated phosphorylation of PKCζ/λ, but not Akt or ERK, proteins. EGCG inhibited IGF stimulation of 3T3-L1 adipocyte glucose uptake through downregulated GLUT4 translocation and IGF signaling by the 67LR- and AMPK-dependent pathways. Results of this dissertation would help explain the mechanisms of how EGCG regulates insulin-, IGF-I-, and IGF-II-mediated actions on fat cells and how it exerts its antiobese effect.

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