title: Insulin signaling: a potential signaling pathway for the stimulatory effect of kaempferitrin on glucose uptake in skeletal muscle.
abstract: The aim of the study was to investigate the in vitro effect and the mechanism of action of kaempferitrin on glucose uptake in an insulin target (soleus muscle). A stimulatory effect of kaempferitrin on glucose uptake was observed when rat soleus muscle was incubated with 10, 100 and 1000 ηM of this flavonoid glycoside. The presence of specific insulin signaling inhibitors, such as wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, an inhibitor of mitogen-activated protein kinase (MEK), HNMPA(AM)3, an insulin receptor tyrosine kinase activity inhibitor, colchicine, a microtubule-depolymerizing agent, SB239063, an inhibitor of P38 MAPK and cycloheximide, an inhibitor of protein synthesis showed that kaempferitrin triggers different metabolic and nuclear pathways in skeletal muscle. Besides the influence on glycogen storage, the metabolic action involves the insulin receptor, PI3K, atypical PKC activity and the translocation of GLUT4. Additionally, the nuclear pathways (via MAPK and MEK) provide evidence of the stimulation of the expression of glucose transporters or other signaling proteins, reinforcing proposals that skeletal muscle represents a primary site at which kaempferitrin exerts its effect promoting glucose homeostasis. Also, these similarities with the signaling pathways of insulin constitute strong evidence for the insulin-mimetic role of kaempferitrin in glucose homeostasis.
authors: Universidade Federal da Fronteira Sul, Campus Universitário Laranjeiras do Sul, Bairro Vila Alberti, CEP 85303-775, Laranjeiras do Sul, PR, Brazil.
authors: Luisa Helena
authors: LH
authors: Cazarolli
authors: Danielle Fontana
authors: DF
authors: Pereira
authors: Virginia Demarchi
authors: VD
authors: Kappel
authors: Poliane
authors: P
authors: Folador
authors: Maria dos Santos Reis Bonorino
authors: Mdos S
authors: Figueiredo
authors: Moacir Geraldo
authors: MG
authors: Pizzolatti
authors: Fátima Regina Mena Barreto
authors: FR
authors: Silva
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D044949:Kaempferols / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007328:Insulin; D044949:Kaempferols; D005947:Glucose; C042728:lespenefril