Insulin-feedback via PI3K-C2α activated PKBα/Akt1 is required for glucose-stimulated insulin secretion

摘要: Phosphatidylinositide 3-kinases (PI3Ks) play central roles in insulin signal transduction. While the contribution of class Ia PI3K members has been extensively studied, role II remains poorly understood. The diverse actions PI3K-C2alpha have attributed to its lipid product PI(3)P. By applying pharmacological inhibitors, transient overexpression and small-interfering RNA-based knockdown PKB/Akt isoforms, together with PI-lipid profiling live-cell confocal total internal reflection fluorescence microscopy, we now demonstrate that response insulin, generates PI(3,4)P(2), which allows selective activation PKBalpha/Akt1. Knockdown expression subsequent reduction PKBalpha/Akt1 activity pancreatic beta-cell impaired glucose-stimulated release, at least part, due reduced glucokinase increased AS160 activity. Hence, our results identify transduction via as a novel pathway whereby activates thus discloses potential drugable target type 2 diabetes. high degree codistribution receptor B type, but not A same plasma membrane microdomains lends further support concept selectivity signaling is achieved by spatial segregation events.