Insulin-like effects of vanadate on glucose uptake and on maturation in Xenopus laevis oocytes.
Vanadate, an inhibitor of phosphotyrosyl phosphatases that exerts insulin-like effects in intact cells, stimulated both maturation and glucose uptake in isolated Xenopus laevis oocytes. Vanadate enhanced the effects of insulin/IGF-I and progesterone on maturation in a dose-dependent manner, with an effective concentration of 750 microM and a maximum at 2 mM, whereas, in the absence of hormone, activation of maturation was seen at 10 mM vanadate. Further, vanadate at 2 mM increased glucose uptake, but this effect was not additive to that of the hormone. In cell-free systems, vanadate caused a 12-fold stimulation of autophosphorylation of the oocyte IGF-I receptor in the absence, but not in the presence, of IGF-I and inhibited largely, but not totally, receptor dephosphorylation induced by an extract of oocytes rich in phosphotyrosyl phosphatase activities. These effects were dose dependent, with effective concentrations of 50-100 microM and maxima at 2 mM. Moreover, using an acellular assay to study the effect of vanadate on the activation of maturation promoting factor (MPF), we found that vanadate at 2 mM stimulated the activation of the MPF H1 kinase. This suggests that vanadate did not prevent dephosphorylation of p34cdc2 on tyrosine residues. Vanadate thus exerted insulin-like effects in oocytes, including stimulation of maturation. These effects might result from a direct or indirect action of vanadate on the IGF-I receptor kinase and on MPF activity.
Hainaut
P
P
Institut National de la Santé et de la Recherche Médicale, U145 Faculté de Médecine, Nice, France.
Giorgetti
S
S
Kowalski
A
A
Van Obberghen
E
E
D000818:Animals; D002474:Cell-Free System; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D016200:Maturation-Promoting Factor / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology; D015398:Signal Transduction; D014638:Vanadates / Q000494:pharmacology*; D014982:Xenopus laevis
D007328:Insulin; D014638:Vanadates; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D016200:Maturation-Promoting Factor; D005947:Glucose