Signaling pathways of kaempferol-3-neohesperidoside in glycogen synthesis in rat soleus muscle.
Kaempferol 3-neohesperidoside is one of the several compounds that have been reported to have insulin-like properties in terms of glucose lowering. We studied the effect of kaempferol 3-neohesperidoside in glycogen synthesis in rat soleus muscle through the incorporation of (14)C-d-glucose in glycogen. Kaempferol 3-neohesperidoside stimulates glycogen synthesis in rat soleus muscle by approximately 2.38-fold. Insulin at 100 nM showed a stimulatory effect on glycogen synthesis when compared with the control group. The stimulatory effect of kaempferol 3-neophesperidoside on glycogen synthesis was inhibited by wortmannin, the phosphatidylinositol 3-kinase (PI3K) inhibitor, and enhanced by lithium chloride, a glycogen synthase kinase 3 (GSK-3) inhibitor. Moreover, the stimulatory effect of kaempferol 3-neohesperidoside was also nullified by PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK) and by calyculin A, an inhibitor of protein phosphatase 1 (PP1) activity. It was concluded that the PI3K - GSK-3 pathway and MAPK - PP1 pathway are involved in the stimulatory kaempferol 3-neohesperidoside effect on glycogen synthesis in rat soleus muscle.
Departamento de Bioquímica, Centro de Ciências Biológicas, UFSC, Campus Universitário, Bairro Trindade. Cx. Postal 5069, CEP: 88040-970 - Florianópolis, SC, Brazil.
Luisa Helena
LH
Cazarolli
Poliane
P
Folador
Moacir Geraldo
MG
Pizzolatti
Fátima Regina
FR
Mena Barreto Silva
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006003:Glycogen / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D044949:Kaempferols / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D008387:Marine Toxins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin
D000276:Adjuvants, Immunologic; D000730:Androstadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006003:Glycogen; D038362:Glycogen Synthase Kinase 3; D007004:Hypoglycemic Agents; D007328:Insulin; D007329:Insulin Antagonists; D044949:Kaempferols; D018021:Lithium Chloride; D008387:Marine Toxins; D020928:Mitogen-Activated Protein Kinases; D010080:Oxazoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054645:Protein Phosphatase 1; D000077191:Wortmannin; C112732:kaempferol 3-O-neohesperidoside; C059041:calyculin A; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one