In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up.
The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor [IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 [PC-1]; K121Q, insulin receptor substrate [IRS-1]; G972R, insulin receptor substrate 2 [IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 alpha [PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study.
Above all, D-pinitol played a positive role in regulating insulin-mediated glucose uptake in the liver through translocation and activation of the PI3K/Akt signaling pathway in T2DM rats.
IPPKKNQDKTE prevents high glucose-induced insulin resistance in HepG2 cells by modulating the IRS-1/PI3K/Akt signaling pathway through AMPK activation, indicating that IPPKKNQDKTE plays a potential role in the prevention and treatment of hepatic insulin resistance and type 2 diabetes.
Our data showed that real-time polymerase chain reaction and western blot indicated that GA upregulated the level of phosphatidylinositol-3-kinase (PI3K) and glycogen synthesis (GS) and promoted the phosphorylation of protein kinase B (Akt) while downregulated the expression of glycogen synthesis kinase-3β (GSK-3β) in T2DM rats.
Over 35 weeks, this induced classic signs of T2D (hyperglycemia and insulin dysfunction) and a modest, but stable deficit in spatial recognition memory, with very little long-term modification of proteins in or associated with IR/PI3K/Akt signalling in CA1 of the hippocampus.
OP alleviated the T2DM characteristics through the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway, and enhanced the nuclear factor erythroid-2 (Nrf2) expression and promoted Nrf2-medicated heme oxygenase-1(HO-1) and superoxide dismutase 2 (SOD2) expression.
Increased activity of PI3K/AKT and decreased activity of GSK-3β were detected in hippocampus of T2D+CAP group compared with T2D group, and these changes did not show in T2D+PF group either.
In the present study, we studied the expression of Foxo1, Gsk3β and PI3K-Akt-mTOR in the brain of streptozotocin-induced type 2 diabetes mellitus Wistar rats.
Western blot analysis indicated that the up-regulated IRS1-PI3K-Akt phosphorylation followed by the down-regulated FoxO1/GSK 3β phosphorylation contributed to the enhanced glycogen synthesis and the decreased gluconeogenesis by GXG, suggesting that the response of insulin-mediated IRS1-PI3K-Akt-FoxO1/GSK 3β signaling to GXG might be the required mechanism for GXG-ameliorated development of type 2 diabetes.
Upregulation of SLAMF3 on human T cells is induced by palmitic acid through the STAT5-PI3K/Akt pathway and features the chronic inflammatory profiles of type 2 diabetes.
Tangganjian decoction ameliorates type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats by activating the IRS/PI3K/AKT signaling pathway.
We demonstrate, at a mechanistic level, how the insulin signaling pathway is related to other significant AD pathways such as the neurotrophin signaling pathway, PI3K/AKT signaling, MTOR signaling, and MAPK signaling and how these pathways do cross-talk with each other both in AD and T2DM.
PI3K/AKT pathway damaged in various tissues of the body leads to obesity and type 2 diabetes as the result of insulin resistance, and in turn, insulin resistance exacerbates the PI3K/AKT pathway, forming a vicious circle.
Berberine significantly attenuated memory impairment, axonopathy, and tau hyperphosphorylation, and also restored PI3K/Akt/GSK3β signaling pathway in T2D rats.
Interestingly, this subpopulation also revealed several miRNAs with predicted targets in the PI3K/Akt pathway, not previously described in relation to T2DM muscle dysfunction.
Skeletal muscle insulin resistance, decreased phosphatidylinositol 3-kinase (PI3K) activation and altered mitochondrial function are hallmarks of type 2 diabetes.