@entity3190 ( @entity3190 ) and insulin resistance (IR) are frequently associated with @entity101 and @entity731 . However, the exact roles of @entity3190 and IR in the development of @entity101 are unclear. Mitogen-activated protein kinases (MAPK) are well-characterized intracellular mediators of cell proliferation. In this study, we examined the contribution of MAPK pathway in insulin-stimulated mitogenesis using primary vascular smooth muscle cells (VSMCs) isolated from aortas of normotensive @entity35 -Kyoto @entity35 (WKY) and spontaneous @entity101 @entity35 (SHR). VSMCs were grown to confluence in culture, serum starved, and examined for DNA synthesis (using @entity665 (TDR), immunoprecipitated MAPK activity, and MAPK phosphatase ( @entity53044 ) induction). Basal rate of TDR incorporation into DNA was twofold higher in SHR compared with WKY (P < 0.005). Insulin caused a dose-dependent increase in TDR incorporation (150% over basal levels with 100 nM in 12 h). Stimulation was sustained for 24 h with a decline toward basal in 36 h. Pretreatment with @entity2135 ( @entity7814 antibody did not abolish mitogenesis mediated by 10-100 nM insulin, suggesting that insulin effect is mediated via its own receptors. Insulin had a small mitogenic effect in WKY (33% over basal). Insulin-stimulated mitogenesis was accompanied by a dose-dependent increase in MAPK activity in SHR, with a peak activation (>2-fold over basal) between 5 and 10 min with 100 nM insulin. Insulin had very small effects on MAPK activity in WKY. In contrast, serum-stimulated MAPK activation was comparable in WKY and SHR. Pretreatment with MEK inhibitor, @entity4286 , completely blocked insulin's effect on MAPK activation and mitogenesis. Inhibition of @entity4357 3-kinase with @entity2307 also prevented insulin's effects on MAPK activation and mitogenesis. In WKY, insulin and @entity2135 treatment resulted in a rapid induction of @entity53044 , the dual-specificity MAPK phosphatase. In contrast, VSMCs from SHR were resistant to insulin with respect to MPK-1 expression. We conclude that insulin is mitogenic in SHR, and the effect appears to be mediated by sustained MAPK activation due to impaired insulin-mediated @entity53044 mRNA expression, which may act as an inhibitory feedback loop in attenuating MAPK signaling.

Vascular smooth muscle cell growth and insulin regulation of mitogen-activated protein kinase in XXXX .

@entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension', 'hypertensive'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD-98059'] @entity2307 :: ('MESH:C009687', 'Chemical') :: ['wortmannin'] @entity665 :: ('CHEBI:53526', 'Chemical') :: ['[3H]thymidine'] @entity3190 :: ('MESH:D006946', 'Disease') :: ['Hyperinsulinemia', 'HI'] @entity2135 :: ('24482(Tax:10116)', 'Gene') :: ['insulin-like growth factor I', 'IGF-I'] @entity53044 :: ('114856(Tax:10116)', 'Gene') :: ['MKP-1'] @entity35 :: ('10116', 'Species') :: ['Wistar', 'rats'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity7814 :: ('25718(Tax:10116)', 'Gene') :: ['IGF-I) receptor']
@entity101 :: (MESH:D006973,Disease) :: ['hypertension']
