巨噬細胞對於脂肪細胞胰島素訊息傳遞及葡萄糖代謝的影響

肥胖屬於低度慢性的發炎反應，主要機制是堆積在脂肪細胞當中的巨噬細胞釋放特定細胞激素而導致脂肪細胞處於持續的發炎狀態，而這也是脂肪細胞產生胰島素阻抗性的重要原因。巨噬細胞可能因不同刺激而分化成不同的表現型，進而對脂肪細胞的胰島素訊息傳遞及葡萄糖的代謝產生不同影響，故本研究將探討各種不同表現型的巨噬細胞(M0、M1及M2)對於脂肪細胞胰島素訊息傳遞調控蛋白insulin receptor substrate 1 (IRS1), p85 regulatory subunit of phosphoinositide 3-kinase (p85 PI3K) 及protein kinase B (PKB/ AKT)表現量，以及胰島素活化AKT後所調控的的肝醣合成相關蛋白glycogen synthase kinase3 (GSK3)及glycogen synthase(GS)表現量的影響。由實驗結果得知脂肪前驅細胞加入M1-conditioned medium後，p-IRS1, PI3K, p-AKT的表現量以及胰島素刺激的肝醣合成增加，而當加入M2-conditioned medium後成熟脂肪細胞當中的PI3K , p-AKT表現量有增加的情形。由此推論，不同表現型的巨噬細胞所釋放出來的細胞激素會影響脂肪細胞中的胰島素訊息傳遞以及肝醣的合成。3T3-L1 conditioned medium可促使巨噬細胞分化成M1促發炎型巨噬細胞。以上結果將有助於了解脂肪細胞與巨噬細胞之間的交互作用，但未來仍需進行更多實驗以進一步地釐清相關機制。

關鍵字

肥胖；脂肪細胞；巨噬細胞；胰島素阻抗

並列摘要

Obesity is a low-grade inflammation and is characterized by inflammatory cytokines from the accumulation of adipose tissue macrophage that can lead to insulin resistance. Different types of macrophages may affect the insulin signaling and glucose metabolism of adipose tissue. In this study, we used conditioned mediums from different types of macrophages (M0, M1 and M2) to test their effects to insulin signaling of 3T3-L1 adipocytes, including the expression and phosphorylation level of regulatory protein like insulin receptor substrate 1 (IRS1), p85 regulatory subunit of phosphoinositide 3-kinase (p85 PI3K), protein kinase B (PKB/AKT) and glycogen synthesis regulatory protein including glycogen synthase kinase 3 (GSK3) and glycogen synthase (GS). Our data showed that the protein levels of p-IRS1, PI3K, p-AKT and GS in 3T3-L1 preadipocyte were increased in the presence of M1-conditioned medium. But the protein levels of PI3K and p-AKT in mature 3T3-L1 adipocyte were increased in the presence of M2-conditioned medium. It is indicated the conditioned medium of macrophage may contain certain secretory factors to affect the insulin signaling in adipocytes and interfere glycogen synthesis. 3T3-L1 conditioned medium also affect the differentiation state from M0 to M1. The detail molecular mechanism of this phenomenon is under further investigation.

並列關鍵字

obesity ； adipocyte ； macrophage ； insulin resistant

參考文獻

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巨噬細胞對於脂肪細胞胰島素訊息傳遞及葡萄糖代謝的影響

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