It’s abundantly clear that glucocorticoids do activate SGK in H cells plus the fact the physiological results of glucocorticoid stimulation are reproduced by transient expression of a constitutively active type of SGK recommend strongly that this kinase is involved in this response . On the other hand, our information also display that SGK is energetic in hormone deprived cells, despite the truth that GNa is negligible and it truly is far from clear why this basal exercise of SGK is not transduced into a Na absorbing phenotype . Also, transient expression of a dominant negative SGK mutant suppresses the glucocorticoid induced activation of the endogenous kinase without the need of blocking the related rise in GNa and these findings , in frequent with the current information, propose that signalling by way of PIK SGK is simply not significant to your control of ENaC function. It truly is so exciting that steroid hormones induce the expression of a quantity of other proteins that seem to be involved with the hormonal control of GNa.
As an example, aldosterone evokes expression of your protein encoded by n myc downstream regulated gene and this protein has informative post been shown to increase the exercise of ENaC expressed in Xenopus oocytes and Fisher rat thyroid cells . Steroid hormones also induce expression of glucocorticoid inducible leucine zipper proteins as well as a increasing physique of proof implicates these proteins from the manage of ENaC function . Interestingly, current work has suggested that GILZ may act in cooperation with SGK and established that transient expression of GILZ mimics the electrophysiological results of glucocorticoid stimulation in H cells . It can be hence doable that these mechanisms may perhaps contribute towards the maintenance of basal Na transport in hormonedeprived mpkCCD cells.
Insulin induced Na transport Insulin acutely stimulated Na absorption and induced phosphorylation of PKB Ser, NDRG Thr and PRAS Ser, indicating that this hormone activates PIK and in addition increases the action on the downstream Tanshinone IIA protein kinases SGK and PKB. Despite the fact that we’ve got assumed that these responses to insulin are mediated through genuine insulin receptors, we cannot exclude the chance that these results may possibly be mediated, a minimum of in portion, via receptors for insulin like growth issue , as the concentration of insulin made use of here may possibly make it possible for activation of these receptors . Having said that, IGF and insulin are imagined to manage Na transport by means of really related mechanisms and, whilst wortmannin, PI and GDC had differing effects on basal IEq , these compounds all caused primarily comprehensive inhibition of insulin induced Na absorption and abolished the insulin induced phosphorylation of endogenous proteins.
Whilst signalling by means of PIK SGK does not appear to be critical in the maintenance of basal Na absorption , our information suggest strongly that this signalling pathway is crucial to insulin induced Na transport.