GLUT4 상향조절을 통한 Allium hookeri 추출물의 3T3-L1 세포 내 포도당 흡수 증진 효과

Abstract

삼채(Allium species)는 전통적인 약재나 건강 증진 식품으로 사용되어 왔다. 특히, Allium hookeri (A. hookeri)는 제 2형 당뇨병 모델 마우스에서 혈당 감소 효과가 보고되었다. 본 연구에서는 A. hookeri 추출물이 3T3-L1 세포에서 인슐린 민감성을 증진시키는지 시험하였다. 3T3-L1 지방세포분화가 불완전하게 유도되는 저농도의 인슐린 조건에서, A. hookeri 추출물은 세포 내 지방 함량을 증가시키고, 분화 유도 전사인자인 <TEX>$PPAR{\gamma}$</TEX>의 발현을 상승시켰다. 또한, A. hookeri 추출물은 포도당 수송체 4(GLUT4)의 발현을 증가시킴으로써 세포 내 포도당 흡수(glucose uptake)를 향상시켰다. 이러한 결과들은 A. hookeri 추출물이 인슐린 민감성을 증진시켜 <TEX>$PPAR{\gamma}$</TEX>와 GLUT4를 활성화하고, 세포 내 포도당 흡수를 촉진한다는 사실을 보여준다. 따라서, A. hookeri 추출물은 당뇨병의 예방 및 치료에 임상적으로 응용될 수 있을 것으로 생각된다. Diabetes mellitus is associated with insulin resistance, which leads to down-regulation of insulin signaling and the decreased glucose uptake. Adipocytes are sensitive to insulin, and closely implicated in insulin resistance and diabetes. Insulin stimulates differentiation of preadipocytes to adipocytes, and increases glucose transport. Allium species have been used as traditional medicine and health-promoting foods. Allium hookeri (A. hookeri) is reported to improve the pancreatic <TEX>${\beta}-cell$</TEX> damage and exhibit pancreatic anti-inflammatory activity in streptozotocin-induced diabetic rats. We investigated whether A. hookeri extract (AHE) may stimulate glucose uptake in adipocytes through increasing insulin sensitivity. AHE enhanced fat accumulation, a differentiation biomarker, under the partial induction of differentiation by insulin. <TEX>$PPAR{\gamma}$</TEX>, a transcription factor highly expressed in adipocytes, promotes adipocyte differentiation and insulin sensitivity. AHE increased the differentiation of preadipocytes through up-regulation of <TEX>$PPAR{\gamma}$</TEX>. The activation of <TEX>$PPAR{\gamma}$</TEX> increases the GLUT4 expression during adipocyte differentiation. GLUT4 is responsible for glucose uptake into the adipocytes. AHE increased the expression of GLUT4 in adipocytes, and subsequently enhanced the insulin-stimulated glucose uptake. These results suggest that AHE promotes adipocyte differentiation through activation of <TEX>$PPAR{\gamma}$</TEX>, and leads to enhance glucose uptake in adipocytes along with GLUT4 up-regulation. Thus, AHE may be effective for the insulin-sensitizing and anti-diabetic activities.