Insulinomimetic effect of kaempferol 3-neohesperidoside on the rat soleus muscle.
A stimulatory effect of kaempferol 3-neohesperidoside ( 1) on glucose uptake (35% and 21%) was observed when the rat soleus muscle was incubated with 1 and 100 nM of this flavonoid glycoside, respectively. The concentration-response curve of insulin showed a stimulatory effect at 3.5 and 7.0 nM (42% and 50%) on glucose uptake when compared with the control group. The effect of 1 on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC). However, no significant change occurred on glucose uptake stimulated by 1 when muscles were pretreated with PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and cycloheximide, an inhibitor of protein synthesis. Compound 1 and insulin (7 nM) did not show a synergistic effect on glucose uptake. Additionally, 100 mg/kg of 1 by oral gavage was able to increase glycogen content in the muscle. These results suggest that 1 stimulates glucose uptake in the rat soleus muscle via the PI3K and PKC pathways and, at least in part, independently of MEK pathways and the synthesis of new glucose transporters.
Zanatta
Leila
L
Departamento de Bioquímica, Campus Universitário, Bairro Trindade, Florianópolis, SC, Brazil.
Rosso
Angela
A
Folador
Poliane
P
Figueiredo
Maria S R B
MS
Pizzolatti
Moacir G
MG
Leite
Laura D
LD
Silva
Fátima R M B
FR
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis* / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004195:Disease Models, Animal; D029624:Ferns / Q000737:chemistry*; D006003:Glycogen / Q000032:analysis; D007328:Insulin / Q000494:pharmacology*; D044949:Kaempferols / Q000494:pharmacology*; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000187:drug effects*; D010946:Plants, Medicinal / Q000378:metabolism*; D051381:Rats
D001786:Blood Glucose; D007328:Insulin; D044949:Kaempferols; C112732:kaempferol 3-O-neohesperidoside; D000496:Alloxan; D006003:Glycogen