Mechanism of action of the stimulatory effect of apigenin-6-C-(2''-O-alpha-l-rhamnopyranosyl)-beta-L-fucopyranoside on 14C-glucose uptake.
There has been a growing interest in hypoglycemic agents from natural products, particularly those derived from plants. Flavonoids are naturally occurring phenolic compounds with a broad range of biological activities and the beneficial effects of flavonoids have been studied in relation to diabetes mellitus, either through their capacity to avoid glucose absorption or to improve glucose tolerance. The purpose of this study was to investigate the mechanism of action of the stimulatory effect of apigenin-6-C-(2''-O-alpha-L-rhamnopyranosyl)-beta-L-fucopyranoside (1), isolated from Averrhoa carambola L. (Oxalidaceae) leaves, on (14)C-glucose uptake. This compound (1) was found to have an acute effect on blood glucose lowering in diabetic rats and stimulated glucose-induced insulin secretion after oral treatment in hyperglycemic rats. A significant stimulatory effect of compound 1 on (14)C-glucose uptake was observed at 50 and 100 microM. The effect of compound 1 on glucose uptake was completely nullified by wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK), cycloheximide, an inhibitor of protein synthesis, and colchicine, a microtubule-depolymerizing agent. Compound 1 (100 microM) and insulin (10 nM) did not show any synergistic effect on glucose uptake. These results suggest that the flavonoid may have a dual target of action, as an insulin-secretagogue and also as an insulin-mimetic agent.
Cazarolli
Luisa Helena
LH
Departamento de Bioquímica, Centro de Ciências Biológicas, UFSC, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970 Florianópolis, SC, Brazil.
Folador
Poliane
P
Moresco
Henrique Hunger
HH
Brighente
Inês Maria Costa
IM
Pizzolatti
Moacir Geraldo
MG
Silva
Fátima Regina Mena Barreto
FR
D000496:Alloxan / Q000008:administration & dosage; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D019684:Magnoliopsida / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D000077191:Wortmannin
D000730:Androstadienes; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D004187:Disaccharides; D047309:Flavones; D005419:Flavonoids; D007211:Indoles; D007328:Insulin; C540362:apigenin-6-C-(2''-O-rhamnopyranosyl)-fucopyranoside; D000496:Alloxan; D003513:Cycloheximide; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D003078:Colchicine; C064758:Ro 31-8220; D000077191:Wortmannin