[논문]후코이단의 3T3-L1 지방세포에서 PI3K/AMPK 경로를 통한 포도당 흡수 촉진 및 인슐린 민감성 증진 효과

이지희; 박재은; 한지숙

doi:10.5352/jls.2021.31.1.1

후코이단의 3T3-L1 지방세포에서 PI3K/AMPK 경로를 통한 포도당 흡수 촉진 및 인슐린 민감성 증진 효과
Fucoidan Stimulates Glucose Uptake via the PI3K/AMPK Pathway and Increases Insulin Sensitivity in 3T3-L1 Adipocytes 원문보기

생명과학회지 = Journal of life science, v.31 no.1, 2021년, pp.1 - 9

이지희 (부산대학교 생활과학대학 식품영양학과) , 박재은 (부산대학교 생활과학대학 식품영양학과) , 한지숙 (부산대학교 생활과학대학 식품영양학과)

초록
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본 연구는 갈조류 유래 물질인 후코이단이 인슐린 민감성을 증진시키는지를 규명하기 위하여 3T3-L1 지방세포에서 포도당 흡수에 미치는 후코이단의 영향을 측정하고 그 작용기전을 조사하였다. 후코이단은 지방세포에서 포도당 흡수를 유의하게 증가시켰으며 이는 PM-GLUT4의 발현 증가와 관련이 있음을 관찰하였다. 후코이단은 인슐린 신호전달 경로에서 PI3K의 활성화 및 pIRS1tyr, Akt, PKCλ/ζ의 인산화를 대조군에 비해 유의하게 증가시켰다. 또한, AMPK의 활성화를 나타내는 pAMPK 수준이 유의하게 증가하였다. 이들 PI3K 및 AMPK 활성화는 포도당 수송체인 GLUT4를 세포막으로 이동시켰으며 이로 인하여 PM-GLUT4의 발현이 증가되고 포도당 흡수가 촉진되었다. 후코이단에 의한 PI3K 및 AMPK 경로의 활성화를 증명하기 위해, PI3K 억제제인 Wortmannin과 AMPK의 억제제인 Compound C를 사용하여 이들 처리에 의한 포도당 흡수능과 PM-GLUT4의 발현을 측정한 결과 이들의 발현이 유의하게 저해되었다. 따라서 후코이단은 3T3-L1 지방세포에서 PI3K 및 AMPK 경로를 활성화시킴으로써 인슐린 민감성을 증진하고 포도당 흡수를 촉진시킬 수 있음을 나타내었다.

Abstract ▼ AI-Helper

Brown seaweeds have been shown to decrease blood glucose levels and improve insulin sensitivity previously. In this study, we investigated the effect of fucoidan, a complex polysaccharide derived from brown seaweeds, on glucose uptake to improve insulin resistance, and examined its mechanism of action in 3T3-L1 adipocytes. We observed that fucoidan significantly increased glucose uptake and it was related to an increased expression of plasma membrane-glucose transporter 4 (PM-GLUT4) in 3T3-L1 adipocytes. Fucoidan treatment increased the activation of phosphatidylinositol-3-kinase (PI3K) and the phosphorylation of insulin receptor substrate 1 (IRS1tyr) compared with that of the control cells. Fucoidan also promoted the phosphorylation of Akt and protein kinase C (PKC)-λ/ζ compared to that of the control cells. Moreover, fucoidan significantly upregulated acetyl-CoA-carboxylase (ACC) and adenosine monophosphate - activated protein kinase (AMPK) phosphorylation. As a result, translocation of GLUT4 was significantly enhanced in 3T3-L1 adipocytes, which significantly promoted glucose uptake via the PI3K/AMPK pathways. The elevation of glucose uptake by fucoidan was blocked by inhibitor of PI3K and inhibitor of AMPK in 3T3-L1 adipocytes. These findings indicate that fucoidan might ameliorate glucose uptake through GLUT4 translocation to the plasma membrane by activating the PI3K/Akt and AMPK pathways in 3T3-L1 adipocytes. Fucoidan is thought to be of high material value to diabetes treatments and functional foods.

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표/그림 (7)

그림 Fig. 1. Typical structure of fucoidan and effect of fucoidan on glucose uptake in 3T3-L1 adipocytes. (A) Structure of fucoidan. (B) The 3T3-L1 adipocytes were treated with 5, 10, 15, and 20 μM of fucoidan for 24 hr prior to the glucose uptake assay. Data are presented as mean ± SD of three experiments. Statistical analysis was performed by Duncan's multiple range test, and ^a-evalues with different superscript letters are significantly dissimilar (p<0.05).
그림 Fig. 2. Effect of fucoidan on expression of IRS-1/PI3K in 3T3-L1 adipocytes. After 24 hr of incubation with 10 or 20 μM fucoidan or 100 nM insulin, the 3T3-L1 adipocytes were lysed and analyzed by immunoblotting. (A) Phosphorylation level of insulin receptor substrate 1 (IRS-1). (B) Activation levels of phosphatidylinositol-3-kinase (PI3K). Data are presented as mean ± SD of three experiments. Statistical analysis was performed by Duncan's multiple range test, and ^a-dvalues with different super-script letters are significantly dissimilar (p<0.05).
그림 Fig. 3. Effect of fucoidan on expression of Akt/PKC λ/ζ in 3T3-L1 adipocytes. After 24 hr of incubation with 10 or 20 μM fucoidan or 100 nM insulin, the 3T3-L1 adipocytes were lysed and analyzed by immunoblotting. (A) Phosphorylation level of Akt. (B) Phosphorylation level of protein kinase C-λ/ζ (PKCλ/ζ). Data are presented as mean ± SD of three experiments. Statistical analysis was performed by Duncan's multiple range test, and ^a-dvalues with different superscript letters are significantly dissimilar (p<0.05).
그림 Fig. 4. Effects of fucoidan on expression of AMPK/ACC in 3T3-L1 adipocytes. After 24 hr of incubation with 10 or 20 μM fucoidan or 0.5 mM AICAR(AMPK activator), the 3T3-L1 adipocytes were lysed and analyzed by immunoblotting. (A) Phosphorylation level of AMPK. (B) Phosphorylation level of ACC. Data are presented as mean ± SD of three experiments. Statistical analysis was performed by Duncan's multiple range test, and ^a-dvalues with different superscript letters are significantly dissimilar (p<0.05).
그림 Fig. 5. Effects of fucoidan on expression of PM-GLUT4 protein in 3T3-L1 adipocytes. After 24 hr of incubation with 20 μM fucoidan, 100 nM insulin, 20 μM fucoidan + 10 μM compound C (CC), or 20 μM wortmannin (WM), the 3T3-L1 adipocytes were extracted and analyzed by immunoblotting. Data are presented as mean ± SD of three experiments. Statistical analysis was performed by Duncan's multiple range test, and ^a-dvalues with different superscript letters are significantly dissimilar (p<0.05).
그림 Fig. 6. Effects of fucoidan combined with compound C and wort-mannin on glucose uptake in 3T3-L1 adipocytes. The 3T3-L1 adipocytes were incubated with 20 μM fucoidan, 20 μM fucoidan + 10 μM compound C (CC), or 20 μM wortmannin (WM), and then glucose uptake was meas-ured. Data are expressed as mean ± SD of three experi-ments. Statistical analysis was performed by Duncan's multiple range test, and ^a-bvalues with different super-script letters are significantly dissimilar (p<0.05).
그림 Fig. 7. Proposed mechanism by which fucoidan effects glucose uptake via IRS/PI3K and AMPK signaling. Fucoidan in-creases glucose uptake as the result of enhanced PM-GLUT4 expression through the activation of the IRS/ PI3K and AMPK pathways.

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데이터처리

Significant differences between data were determined using Duncan’s multiple range tests.

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