title: Kaempferitrin inhibits GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes.
abstract: Insulin stimulated GLUT4 (glucose transporter 4) translocation and glucose uptake in muscles and adipocytes is important for the maintenance of blood glucose homeostasis in our body. In this paper, we report the identification of kaempferitrin (kaempferol 3,7-dirhamnoside), a glycosylated flavonoid, as a compound that inhibits insulin stimulated GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes. In the absence of insulin, we observed that addition of kaempferitrin did not affect GLUT4 translocation or glucose uptake. On the other hand, kaempferitrin acted as an inhibitor of insulin-stimulated GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes by inhibiting Akt activation. Molecular docking studies using a homology model of GLUT4 showed that kaempferitrin binds directly to GLUT4 at the glucose transportation channel, suggesting the possibility of a competition between kaempferitrin and glucose during the transport. Taken together, our data demonstrates that kaempferitrin inhibits GLUT4 mediated glucose uptake at least by two different mechanisms, one by interfering with the insulin signaling pathway and the other by a possible competition with glucose during the transport.
authors.affiliation: School of Biotechnology, Amrita University, Amritapuri P.O., Kollam, Kerala 690525, India.
authors.forename: C N
authors.initials: CN
authors.lastname: Vishnu Prasad
authors.forename: S
authors.initials: S
authors.lastname: Suma Mohan
authors.forename: Asoke
authors.initials: A
authors.lastname: Banerji
authors.forename: Anilkumar
authors.initials: A
authors.lastname: Gopalakrishnapillai
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology*; D044949:Kaempferols / Q000494:pharmacology*; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D007329:Insulin Antagonists; D044949:Kaempferols; C495693:Slc2a4 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C042728:lespenefril