Activation of MAP kinase by insulin and vanadate in adipocytes from young and old rats.
Vanadate has insulin-like effects in adipocytes without stimulating insulin receptor kinase activity. However, it activates IRS-1 associated PI 3-kinase, suggesting that it mimics insulin effects by stimulating signaling elements downstream of PI 3-kinase. Here we analysed the stimulation of MAPK by insulin and vanadate and observed that both elicit a rapid 3.5-4 fold activation which is abolished by wortmannin and PD98059. Simultaneous addition of insulin and vanadate does not result in an additive effect neither on MAPK nor in MEK. Whereas insulin action is transient, vanadate stimulation lasts up to 20 min. In insulin-resistant adipocytes from old rats, insulin stimulates poorly MAPK, whereas a normal activation is achieved with vanadate. We conclude that: (a) insulin and vanadate use a common signaling pathway from PI 3-kinase to MEK and MAPK; (b) vanadate but not insulin, elicits a sustained activation of both enzymes; (c) this pathway is functional in old rat adipocytes.
Molero
J C
JC
Departamento de Biología Molecular, Facultad de Ciencias, Centro de Biología Molecular "Severo Ochoa" (CSIC), Universidad Autónoma, 28049, Madrid, Spain.
Pérez
C
C
Martínez
C
C
Villar
M
M
Andrés
A
A
Fermín
Y
Y
Carrascosa
J M
JM
D017667:Adipocytes / Q000187:drug effects*; D000375:Aging / Q000502:physiology*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000494:pharmacology*; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007328:Insulin; D014638:Vanadates; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin