This is certainly dependant on our observation that the effects of FTI and PTx on Akt phosphorylation are additive. Therefore, added scientific studies are necessary to even more verify the identity of Probin. Our findings also suggest that the two the basal and FTI induced phosphorylation of Akt had been attenuated by PGE, a identified activator of inhibitory class of G proteins; such effects are mediated through PGE receptor . A number of lines of evidence suggest regulatory roles for PGE in islet perform. As an example, using HIT T cells, Robertson and associates have demonstrated the presence of PGE receptors inside the cell membrane fraction, which can be regulated by inhibitory element of adenylate cyclase . Research from Laychock?s laboratory have demonstrated that PGE receptor is coupled to PTx delicate G protein and that the later on was capable of reverse the PGE inhibition of glucose induced insulin secretion . Moreover, research from our laboratory have demonstrated expression of functionally regulable substantial affinity GTPase routines inside the membrane and secretory granule fractions derived from standard rat and human pancreatic islets that may be stimulated by PGE .
Lastly, we’ve got also demonstrated regulation on the carboxylmethylation of Ggsubunits by PGE by way of a PTx sensitive mechanism MAP2K2 inhibitor . Taken with each other, our findings implicate inhibitory class of G proteins during the signaling axis top to FTI mediated activation of Akt in INS cells and typical rat islets. Our findings also suggest that such IGF can directly activate Akt phosphorylation presumably by way of a mechanism not requiring inhibitory G proteins seeing that IGF mediated activation of Akt seems to become resistant to PGE at the very least beneath our recent experimental conditions working with INS cells. Interestingly however, recent studies by Meng and coworkers in HIT T cells demonstrated a significant reduction in basal Akt phosphorylation by PGE, which was reversed by IGF . According to these observations these authors concluded that PGE induces metabolic defects in b cells largely by upregulating the Ptger gene expression and associated down regulation of Akt FoxO signaling cascade.
Our findings are compatible with these observations since PGE markedly reduced basal Akt phosphorylation. Reversal of inhibition of Akt phosphorylation by IGF is hard to assess given that the later on significantly improved phosphorylation of Akt. Nevertheless, our data clearly implicate probable roles for inhibitory class p53 inhibitors of trimeric G proteins in FTI induced phosphorylation of Akt. As while in the situation of Probin, more scientific studies are desired to find out precise identity of those G proteins. Our findings of potential regulatory cross talk among PTx delicate Gi Go proteins and PI kinase Akt signaling mechanisms are compatible with latest observations of Hayakawa and colleagues who demonstrated involvement of Gi Go class of proteins in prolactin releasing peptide mediated activation of Akt signaling pathway in GH rat pituitary cells .