Possible Interaction: Insulin and Phosphatidylinositol 4,5-Diphosphate

“These results suggest that sulphonylureas and insulin induce suppression of thrombin-induced activation of phospholipase C, which mediates hydrolysis of PIP and PIP2 and production of PA, which leads to inhibition of platelet aggregation.”

“Because insulin had little effect on KCNQ1 currents (without KCNE1) in our study, and PI3K can reduce the level of PIP2 by phosphorylation, we hypothesize that PIP2 is a candidate molecule that mediates the suppressive effect of insulin.”

“Our hypothesis for a possible role of PIP2 in the suppressive effect of insulin should be tested.”

“Real-time imaging of single cells showed that treatment with insulin enhances the rate and magnitude of phosphatidylinositol 4,5-bisphosphate hydrolysis and generation of inositol 1,4,5-trisphosphate in response to GPCR stimulation.”

“However, neither inhibitor much increased cellular PtdInsP3 concentrations, but both diminished dramatically the accumulation of PtdInsP3 stimulated by PDGF or insulin and markedly increased the control and stimulated concentrations of PtdIns(3,4)P2.”

“ Insulin treatment promoted an increase in levels of the signaling phospholipid phosphatidylinositol 4,5-bisphosphate ( PIP2 ) in plasmalemmal caveolae.”

“ Insulin induced small, but significant and equal increases (40% at 30 min) in the incorporation of [3H] inositol into phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in adipocytes.”

“It is concluded that insulin increases the synthesis of phosphatidylinositol, phosphatidylinositol 4-phosphate, phosphatidylinositol 4,5-bisphosphate , phosphatidylethanolamine, and phosphatidylserine in fat cells partly by stimulating a reaction(s) located between glycerol 3-phosphate and phosphatidic acid in the biosynthetic pathway.”

“From these data we conclude that insulin stimulates the de novo synthesis of phosphatidylinositol and phosphatidylinositol 4,5-biphosphate , but has no effect on phosphoinositide breakdown.”

“We have previously reported that insulin increases the synthesis de novo of phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) in BC3H-1 myocytes and/or rat adipose tissue.”

“… insulin provoked very rapid increases in PI content (20% within … myocytes) and, after a slight lag, PIP and PIP2 content in both BC3H-1 myocytes and rat fat pads (measured by increases in 32P … after prelabelling phospholipids to constant specific radioactivity by prior incubation with 32Pi or [3H]inositol).”

“SHIP2 (SH2-domain containing inositol 5-phosphatase type 2) is a canonical 5-phosphatase, which, through its catalytic action on PtdInsP3 , regulates the PI3K/Akt pathway and metabolic action of insulin.”