A balanced activation of regulatory subunits of phosphoinositide 3-kinase defines proliferation and survival in pancreatic beta-cells

Protein kinase B (PKB; also known as Akt) is pivotal for beta-cell growth and survival. The main activator of PKB is the lipid kinase phosphinositide 3-kinase (PI3K), which is active as a heterodimer of regulatory and catalytic subunits and may be inhibited by an excess of free regulatory subunits. Alternative splicing of the Pik3r1 gene yields the three PI3K regulatory isoforms p85a, p55a and p50a. Since little is known how PI3K is regulated in pancreatic beta-cells, we examined signalling by p85a, p55a and p50a in insulinoma cells (INS-1E) stimulated by IGF-1. PI3K regulatory isoforms p85a, p55a and p50a were…