RÉSUMÉ
The present study discusses the efficacy of Aloe emodin-8-O-glycoside (AEG), a plant derived anthroquinone, on alleviating insulin resistance and augmenting glycogen synthesis in L6 myotubes and 3T3L1 adipocytes. Dose-dependent increase in glucose uptake activity (GUA) was observed in both cell lines. Immunoblot analysis revealed an insulin-like glucose transporting mechanism of AEG by activating key markers involved in the insulin signaling cascade such as insulin receptor beta IRbeta, insulin receptor substrate1, 85 phosphatidyl inositol 3' kinase (PI3K) and PKB. Glucose transporter 4 translocation was confirmed by determining the uptake of glucose in the presence of insulin receptor tyrosine kinase and PI3K inhibitors. AEG was found to enhance glycogen synthesis through the inhibition of glycogen synthase kinase 3beta. In conclusion, AEG enhances glucose transport by modulating the proximal and distal markers involved in glucose uptake and its transformation into glycogen.
Sujet(s)
Adipocytes/métabolisme , Glucose/métabolisme , Phosphatidylinositol 3-kinases/métabolisme , Animaux , Transport biologique , Métabolisme glucidique , Différenciation cellulaire/effets des médicaments et des substances chimiques , Glycogène/métabolisme , Glycogen Synthase Kinases/métabolisme , Hétérosides/métabolisme , Insuline/métabolisme , Insuline/pharmacologie , Insulinorésistance , Souris , Fibres musculaires squelettiques , Récepteur à l'insuline/métabolismeRÉSUMÉ
Evaluations of molecular mechanisms of dietary plants with their active molecules are essential for the complete exploration of their nutritive and therapeutic value. In the present study, we investigated the effect of chicory (Cichorium intybus) salad leaves in inhibiting protein tyrosine phosphatase 1B (PTP1B), and evaluated their role in modulating the key markers involved in insulin cell signalling and adipogenesis using 3T3-L1 adipocytes. Bioactivity-directed purification studies enlightened the additive effects of chlorogenic acid (CGA) along with other caffeic acid derivatives present in methanolic extract of C. intybus (CME). Incubation of CME and CGA with 3T3-L1 adipocytes significantly enhanced the 2-deoxy-d-3[H]-glucose uptake and inhibited adipogenesis through altering the expressions of insulin signalling and adipogenesis markers. Extending to an in vivo model, the effect of CME was also investigated on insulin sensitivity in high-fat diet with low streptozotocin-induced diabetic rats. Supplementation of CME for 2 weeks reinstated the insulin sensitivity along with plasma metabolic profile. The present results demonstrate that the caffeoyl derivatives of chicory salad leaves show promising pharmacological effect on energy homoeostasis via PTP1B inhibition both in vitro and in vivo.
Sujet(s)
Acides caféiques/pharmacologie , Cichorium intybus/composition chimique , Diabète expérimental/traitement médicamenteux , Hypoglycémiants/pharmacologie , Insuline/métabolisme , Extraits de plantes/pharmacologie , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonistes et inhibiteurs , Cellules 3T3-L1 , Adipocytes/effets des médicaments et des substances chimiques , Adipogenèse/effets des médicaments et des substances chimiques , Animaux , Acides caféiques/usage thérapeutique , Acide chlorogénique/pharmacologie , Acide chlorogénique/usage thérapeutique , Diabète expérimental/métabolisme , Matières grasses alimentaires/administration et posologie , Glucose/métabolisme , Hypoglycémiants/usage thérapeutique , Insulinorésistance/physiologie , Mâle , Souris , Phytothérapie , Extraits de plantes/usage thérapeutique , Feuilles de plante , Rats , Rat Wistar , Transduction du signal/effets des médicaments et des substances chimiquesRÉSUMÉ
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.