Dissociation between Insulin-Mediated Signaling Pathways and Biological Effects in Placental Cells: Role of Protein Kinase B and MAPK Phosphorylation
Beyond the presence of insulin receptors, little is known of the mechanisms underlying the biological effects of insulin in the placenta. We show that phosphorylation of MAPK and protein kinase B were enhanced 286 ± 23% and 393 ± 17% upon insulin stimulation of JAr placental cells. MAPK activation w...
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Veröffentlicht in: | Endocrinology (Philadelphia) 2001-09, Vol.142 (9), p.3974-3979 |
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Zusammenfassung: | Beyond the presence of insulin receptors, little is known of the
mechanisms underlying the biological effects of insulin in the
placenta. We show that phosphorylation of MAPK and protein kinase B
were enhanced 286 ± 23% and 393 ± 17% upon insulin
stimulation of JAr placental cells. MAPK activation was prevented by
pretreatment with PD98059 but was unaffected by wortmannin. Insulin
stimulation of protein kinase B phosphorylation was abolished by
pretreatment with wortmannin, suggesting that it is dependent on
phosphatidylinositol 3- kinase activation. Despite protein kinase B
phosphorylation, GLUT4 translocation, glucose uptake, and glycogen
synthesis were not stimulated by insulin. By contrast, glycogen
synthesis was stimulated 20-fold in cells incubated with 11
mm glucose. Mitogenesis assessed by incorporation of[
3H]thymidine into DNA was enhanced 1.9-fold in response
to insulin. Stimulation of DNA synthesis was inhibited by pretreatment
with PD98059 but was insensitive to wortmannin. These results indicate
that stimulation of mitogenesis is one major biological effect of
insulin in placenta cells that implicates the MAPK signaling pathway.
Phosphatidylinositol 3-kinase- dependent protein kinase B
activation is not sufficient to stimulate glucose transport and
glycogen synthesis, highlighting the placenta as a nonclassic target of
insulin for the regulation of glucose metabolism. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.142.9.8391 |