綠茶表沒食子酸酯型唲茶素酸酯抑制第一型內皮素在短時間和長時間作用於脂肪細胞上的葡萄糖攝入

本研究探討綠茶唲茶素中表沒食子酸酯型唲茶素酸酯(英文為(-)-epigallocatechin gallate，簡寫為EGCG)為是否會調控第一型內皮素(英文為endothelin-1，簡寫為ET-1)在短時間(0.5小時)、中長時間(2小時)和長時間(6小時)刺激脂肪細胞攝入葡萄糖的能力。利用3T3-L1和C3H10T1/2脂肪細胞，實驗中發現，處理2小時的10 μM EGCG能抑制第一型內皮素促進脂肪細胞攝入葡萄糖的能力，並且會抑制第一型內皮素短時間刺激第四型葡萄糖運送蛋白(GLUT-4)從細胞內運送至細胞膜的現象，但EGCG並不影響第一型葡萄糖運送蛋白(GLUT-1)的移動以及第一型葡萄糖運送蛋白和第四型葡萄糖運送蛋白的總蛋白質含量。另外，本研究發現EGCG能抑制第一型內皮素在中長時間和長時間所刺激的葡萄糖攝取以及第一型葡萄糖運送蛋白蛋白質表現量，但並不影響第四型葡萄糖運送蛋白的蛋白質表現量和移動現象。由以上結果說明了，EGCG抑制第一型內皮素在短時間和長時間刺激攝取葡萄糖的能力，可能是分別透過抑制第四型葡萄糖運送蛋白的移動和第一型葡萄糖運送蛋白的蛋白質表現量所導致。進一步的結果發現EGCG能抑制第一型內皮素短時間處理下所刺激的AKT、ERK和STAT-3等訊息分子之磷酸化，並且EGCG也能抑制第一型內皮素在中長時間內所促進的ERK和STAT-3磷酸化現象。有趣的是，長時間的第一型內皮素處理，或者是第一型內皮素和EGCG共同處理，都不會顯著地改變AKT、ERK和STAT-3等蛋白質的磷酸化。此外，當前處理A型內皮素接受器(ETAR)抑制劑BQ-610時，能完全抑制第一型內皮素促進脂肪細胞攝入葡萄糖的能力，並且也能完全抑制第一型內皮素短時間刺激ERK和STAT-3的磷酸化現象。由此可見EGCG會藉由抑制ETAR的下游訊息分子，例如：pAKT、pERK、pSTAT-3，藉此影響第一型內皮素的促進作用。

關鍵字

綠茶；表沒食子酸酯型兒茶素酸酯；第一型內皮素；脂肪細胞；葡萄糖攝入；葡萄糖運送蛋白；訊息傳導路徑

並列摘要

This study investigated whether green tea (-)-epigallocatechin gallate (EGCG) modulated both acute (0.5 h) and chronic (6 h) effects of ET-1 on glucose uptake in adipocytes. Using the 3T3-L1 and C3H10T1/2 adipocytes and [3H]2-deoxyglucose assay, we found that EGCG at 10 μM for 2 h inhibited the acute effect of ET-1 on adipocyte glucose uptake. EGCG was also found to block the acute action of ET-1 on translocation of the glucose transporter-4 (GLUT-4) from the cytosol to the plasma membrane. However, EGCG did not affect the total levels of GLUT-1 or GLUT-4 proteins and had no effects on GLUT-1 translocation. On the other hand, we observed that EGCG prevented the 2-h and chronic effects of ET-1 on adipocyte glucose uptake and GLUT-1 protein expression. However, EGCG did not alter the total levels of GLUT-4 protein and had no effects on the chronically ET-1 altered GLUT-4 translocation. These data suggest that EGCG mediates the acute and chronic effects of ET-1 on adipocyte glucose uptake via the respective alteration of GLUT-4 translocation and GLUT-1 protein expression. Furthermore, EGCG inhibited the acutely ET-1-stimulated phosphorylations of AKT, ERK and STAT-3 signaling molecules. The 2-h stimulation of ERK and STAT-3 phosphorylation by ET-1 was also inhibited by EGCG treatment. Interestingly, treatment with ET-1 for 6 h in the presence and absence of EGCG did not alter any phosphorylation of AKT, ERK, or STAT-3 proteins. Moreover, pretreatment the ETA receptor antagonist, BQ-610, completely inhibited both acute and 2-h effects of ET-1 on glucose uptake and phosphorylation of ERK and STAT-3 in C3H10T1/2 adipocytes. This suggests that EGCG may inhibit the ET-1 action on adipocyte glucose uptake through a similar way to the ETAR downstream signaling molecules.

並列關鍵字

Green tea ； (-)-epigallocatechin gallate ； endothelin-1 ； adipocyte ； glucose uptake ； glucose transporter ； signaling pathway

參考文獻

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2.Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T 1989 The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl. Acad. Sci. U S A 86:2863-2867

3.Kozuka M, Ito T, Hirose S, Lodhi KM, Hagiwara H 1991 Purification and characterization of bovine lung endothelin receptor. J. Biol. Chem. 266:16892-16896

4.Idris I, Patiag D, Gray S, Donnelly R 2001 Tissue- and time-dependent effects of endothelin-1 on insulin-stimulated glucose uptake. Biochem. Pharmacol. 62:1705-1708

6.Wu-Wong JR, Berg CE, Wang J, Chiou WJ, Fissel B 1998 Endothelin stimulates glucose uptake and GLUT4 translocation via activation of endothelin ETA receptor in 3T3-L1 adipocyte. J. Biol. Chem. 274:8103-8110

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綠茶表沒食子酸酯型唲茶素酸酯抑制第一型內皮素在短時間和長時間作用於脂肪細胞上的葡萄糖攝入

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