The mechanistic asis of the dephosphorylation of Akt was found to differ etween phenformin and AICAR. Dephosphorylation TGF-beta of Akt y phenformin treatment was due to lockade of intracellular signaling primary toAkt phosphorylation. Thiswas evident ecause IGF 1 induced Akt phosphorylation, a results of receptor mediated activation of PI3K, was generally based y phenformin. In contrast to themechanismof action of phenformin, AICAR lowered Akt phosphorylation y still another mechanism ecause activation of Akt y IGF 1 was unimpeded y AICAR therapy. A recently available report also found Akt to elizabeth dephosphorylated following AICARtreatment inC6glioma cells, further verifying our conclusion that this is a ro ust effect and it is not cell type specific. However, in those cells it was demonstrated to e through inactivation of PI3K, although our results indicated signaling fromthe IGF 1 receptor through PI3K to Akt wasn’t bothered y AICAR. Therefore, further exploration is required by the inhi itorymechanismof AICAR to e described, ut it may involve activation order Bazedoxifene of phosphatases that are recognized to dephosphorylate Akt. Alternately, inhi ition of other kinases may possibly e involved with the ramifications of AICAR ecause itwas recently noted that AICAR inhi ited the serine 9 phosphorylation of GSK3 caused yco therapy withaphor olesteractivator of protein kinase C plus the calcium ionophore ionomycin. Overall, the differential ramifications of phenformin and AICAR on IGF 1 caused Akt phosphorylation established that the two drugs which normally triggered AMPK caused Akt dephosphorylation b different components. These results extend recent reports of an of phenformin, metformin, where mixed results have een e tained in critiques of its effects on Akt phosphorylation. Treatment with metformin increased insulin induced Akt phosphorylation in cultured HepG2 cells and HGL5 cells, as well as in vivo in rat heart. In comparison, metformin Cholangiocarcinoma reduced Akt phosphorylation stimulated y interleukin 1 or y high sugar, whereas Akt phosphorylation was unaltered y metformin treatment in H4IIE cells and in vivo in dia etic muscle. These mixed results with metformin indicate that context as well as possi le multiple targets of metformin cause this variety of effects on Akt phosphorylation. If this type of varia le result occurs with phenformin awaits further studies, lace within our examination of two distinct cell types, and with oth asal and IGF 1 pleasure, phenformin regularly paid off Akt phosphorylation. Compound Cwas designed as a selective inhi itor ofAMPK and it’s een used in a few studies to decipher cellular effects ofAMPK. Inhi itionofAMPK yCompoundCwas evident in oth hippocampal neurons and SH SY5Y cells b its reduction of the phenformin induced AG-1478 ic50 phosphorylation of ACC, a AMPK su strate popular as an indicator of AMPK initial.