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Raffinose from Costus speciosus attenuates lipid synthesis through modulation of PPARs/SREBP1c and improves insulin sensitivity through PI3K/AKT
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-02-16
Muthukumaran Padmanaban, Thiyagarajan Gopal, Arun Babu Rajendran, Baddireddi Subhadra Lakshmi

Among several metabolic disorders, the pathogenesis of insulin resistance is considered to be multifactorial. Raffinose, an oligosaccharide isolated from the rhizome of Costus speciosus showed ≤50% inhibition of lipid accumulation in differentiated HepG2 and 3T3-L1 cells through exhibiting partial agonism to PPARγ, and, an enhanced secretion of adiponectin in 3T3-L1 adipocytes. Raffinose was also observed to attenuate the expression of SREBP1c, ACC and FAS which are involved in the fatty acid synthesis. A corresponding upregulation of PPARα and ACO involved in fatty acid oxidation was observed in steatotic HepG2 hepatocytes and 3T3-L1 adipocytes. In vitro evaluation of its anti-diabetic potential showed a dose dependent enhancement of glucose uptake. Investigation of the insulin sensitizing efficacy of Raffinose revealed an increase in Glut4 translocation via phosphorylation of IRβ/PI3K/Akt in differentiated L6 myocytes and 3T3-L1 preadipocytes. In addition, Raffinose was potentially involved in glycogen synthesis by inhibiting the activation of GSK3β. Hence, Raffinose could be a useful therapeutic agent for metabolic maladies.



中文翻译:

Costus speciosus的棉子糖通过调节PPAR / SREBP1c减弱脂质合成,并通过PI3K / AKT改善胰岛素敏感性

在几种代谢性疾病中,胰岛素抵抗的发病机理被认为是多因素的。棉子糖,一种从木贼属的根茎中分离得到的寡糖,对PPARγ表现出部分激动作用,从而在分化的HepG2和3T3-L1细胞中显示出≤50%的脂质蓄积抑制作用,并且在3T3-L1脂肪细胞中脂联素分泌增强。还观察到棉子糖可减弱参与脂肪酸合成的SREBP1c,ACC和FAS的表达。在脂肪变性的HepG2肝细胞和3T3-L1脂肪细胞中观察到了与脂肪酸氧化有关的PPARα和ACO的相应上调。体外其抗糖尿病潜力的评估显示了葡萄糖摄取的剂量依赖性增强。对棉子糖的胰岛素增敏功效的研究表明,分化的L6心肌细胞和3T3-L1前脂肪细胞中IRβ/ PI3K / Akt的磷酸化使Glut4易位增加。此外,棉子糖可能通过抑制GSK3β的激活而参与糖原的合成。因此,棉子糖可能是代谢性疾病的有用治疗剂。

更新日期:2018-02-16
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