title: Piceatannol, a resveratrol derivative, promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and suppresses blood glucose levels in type 2 diabetic model db/db mice.
abstract: The skeletal muscle cells are one of the main sites of glucose uptake through glucose transporter 4 (GLUT4) in response to insulin. In muscle cells, 5' adenosine monophosphate-activated protein kinase (AMPK) is known as another GLUT4 translocation promoter. Natural compounds that activate AMPK have a possibility to overcome insulin resistance in the diabetic state. Piceatannol is a natural analog and a metabolite of resveratrol, a known AMPK activator. In this study, we investigate the in vitro effect of piceatannol on glucose uptake, AMPK phosphorylation and GLUT4 translocation to plasma membrane in L6 myocytes, and its in vivo effect on blood glucose levels in type 2 diabetic model db/db mice. Piceatannol was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence. Promotion by piceatannol of glucose uptake as well as GLUT4 translocation to plasma membrane by immunocytochemistry was also demonstrated in L6 myoblasts transfected with a glut4 cDNA-coding vector. Piceatannol suppressed the rises in blood glucose levels at early stages and improved the impaired glucose tolerance at late stages in db/db mice. These in vitro and in vivo findings suggest that piceatannol may be preventive and remedial for type 2 diabetes and become an antidiabetic phytochemical.
authors.affiliation: Department of Applied Life Science, Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Minakawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yagasaki
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057054:Molecular Imaging; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose; D000077185:Resveratrol