Muthusamy V S, Anand S, Sangeetha K N, Sujatha S, Arun Balakrishnan, Lakshmi B S
Centre for Biotechnology, Tissue Culture and Drug Discovery Lab, Anna University, Chennai 600025, Tamilnadu, India.
Chem Biol Interact. 2008 Jul 10;174(1):69-78. doi: 10.1016/j.cbi.2008.04.016. Epub 2008 Apr 24.
Insulin resistance is a fundamental aspect for the etiology of non-insulin dependent diabetes mellitus (NIDDM) and has links with a wide array of secondary disorders including weight gain and obesity. The present study analyzes the effect of Cichorium intybus methanolic (CME) extract on glucose transport and adipocyte differentiation in 3T3-L1 cells by studying the radiolabelled glucose uptake and lipid accumulation assays, respectively. By performing detannification (CME/DT), the role of tannins present in CME on both the activities was evaluated. CME and CME/DT exhibited significant glucose uptake in 3T3-L1 adipocytes with a dose-dependent response. Glucose uptake profile in the presence of PI3K and IRTK inhibitors (Wortmannin and Genistein) substantiates the mechanism used by both the extracts. CME inhibited the differentiation of 3T3-L1 preadipocytes but failed to show glucose uptake in inhibitor treated cells. The activity exhibited by CME/DT is exactly vice versa to CME. Furthermore, the findings from PTP1B inhibition assay, mRNA and protein expression analysis revealed the unique behavior of CME and CME/DT. The duality exhibited by C. intybus through adipogenesis inhibition and PPARgamma up regulation is of interest. Current observation concludes that the activities possessed by C. intybus are highly desirable for the treatment of NIDDM because it reduces blood glucose levels without inducing adipogenesis in 3T3-L1 adipocytes.
胰岛素抵抗是非胰岛素依赖型糖尿病(NIDDM)病因的一个基本方面,并且与包括体重增加和肥胖在内的一系列继发性疾病有关。本研究分别通过研究放射性标记葡萄糖摄取和脂质积累试验,分析了菊苣甲醇提取物(CME)对3T3-L1细胞中葡萄糖转运和脂肪细胞分化的影响。通过进行脱单宁处理(CME/DT),评估了CME中存在的单宁对这两种活性的作用。CME和CME/DT在3T3-L1脂肪细胞中表现出显著的葡萄糖摄取,且呈剂量依赖性反应。在存在PI3K和IRTK抑制剂(渥曼青霉素和染料木黄酮)的情况下的葡萄糖摄取情况证实了两种提取物所采用的机制。CME抑制了3T3-L1前脂肪细胞的分化,但在抑制剂处理的细胞中未能显示出葡萄糖摄取。CME/DT所表现出的活性与CME恰好相反。此外,蛋白酪氨酸磷酸酶1B(PTP1B)抑制试验、mRNA和蛋白表达分析的结果揭示了CME和CME/DT的独特行为。菊苣通过抑制脂肪生成和上调过氧化物酶体增殖物激活受体γ(PPARγ)所表现出的双重性令人关注。目前的观察结果得出结论,菊苣所具有的活性对于治疗NIDDM非常理想,因为它能降低血糖水平,而不会在3T3-L1脂肪细胞中诱导脂肪生成。