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Chem Biol Interact ; 284: 80-89, 2018 Mar 25.
Article in English | MEDLINE | ID: mdl-29458019

ABSTRACT

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 IRß/PI3K/Akt in differentiated L6 myocytes and 3T3-L1 preadipocytes. In addition, Raffinose was potentially involved in glycogen synthesis by inhibiting the activation of GSK3ß. Hence, Raffinose could be a useful therapeutic agent for metabolic maladies.


Subject(s)
Costus/chemistry , Lipid Metabolism/drug effects , Peroxisome Proliferator-Activated Receptors/metabolism , Raffinose/pharmacology , Signal Transduction/drug effects , Sterol Regulatory Element Binding Protein 1/metabolism , 3T3-L1 Cells , Animals , Cell Line , Costus/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Hep G2 Cells , Humans , Insulin Resistance , Lipid Peroxidation/drug effects , Mice , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Up-Regulation/drug effects
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