Insulinomimetic effects of myricetin on lipogenesis and glucose transport in rat adipocytes but not glucose transport translocation.
Myricetin is a naturally occurring flavonol that is commonly found in tea, berries, fruits, and medicinal plants. It mimics insulin in stimulating lipogenesis and glucose transport in rat adipocytes in vitro. It was found to stimulate lipogenesis in rat adipocytes and enhance the stimulatory effect of insulin. The EC50 was estimated to be about 65 microM. Myricetin did not have any effect on insulin receptor autophosphorylation nor on the tyrosine kinase activity of the receptor. However, myricetin stimulated both D-glucose and D-3-O-methylglucose uptake in rat adipocytes. The Vmax of glucose transport was increased, but the Km did not change significantly. Immunoblot analysis of Glut4 in rat adipocyte plasma membrane showed that the stimulation of glucose transport was not a consequence of glucose transporter translocation. Instead, the stimulation in glucose uptake probably was due to a change in the intrinsic activity of the glucose transporter possibly caused by alterations in membrane fluidity or transporter-lipid interactions as a result of the insertion of myricetin into the membrane bilayer. Thus, myricetin may have therapeutic potential in the management of non-insulin-dependent diabetes mellitus by stimulating glucose uptake without the presence of fully functional insulin receptor.
Ong
K C
KC
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Khoo
H E
HE
D019325:3-O-Methylglucose; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004822:Epididymis; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism*
D005419:Flavonoids; D051275:Glucose Transporter Type 4; D007328:Insulin; D008055:Lipids; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; C040015:myricetin; D011972:Receptor, Insulin; D005947:Glucose