Artículos de revistas
Involvement of Phosphatidylinositol-3 Kinase/AKT/PKC zeta/lambda Pathway in the Effect of Palmitate on Glucose-Induced Insulin Secretion
Fecha
2008Registro en:
PANCREAS, v.37, n.3, p.309-315, 2008
0885-3177
10.1097/mpa.0b013e318168dac3
Autor
NOGUEIRA, Tatiane C. A.
ANHE, Gabriel F.
CARVALHO, Carla R. O.
Curi, Rui
BORDIN, Silvana
CARPINELLI, Angelo R.
Institución
Resumen
Objectives: In the present study, a novel pathway by which palmilate potentiates glucose-induced insulin secretion by pancreatic beta cells was investigated. Methods: Groups of freshly isolated islets were incubated in 10 mM glucose with palmitate, LY294002, wortmannin, and fumonism B I for measurement of insulin secretion by radioimmunoassay (RIA). Also, phosphorylation and content of AKT and PKC proteins were evaluated by immunoblotting. Results: Glucose plus palmitate and glucose plus LY294002 or wortmannin (PI3K inhibitors) increased glucose-induced insulin secretion by isolated pancreatic islets. Glucose at 10 mM induced AKT and PKC zeta/lambda phosphorylation. Palmitate (0.1 mM) abolished glucose stimulation of AKT and PKC zeta/lambda phosphorylation possibly through PI3K inhibition because both LY294002 (50 mu M) and wortmannin (100 nM) caused the same effect. The inhibitory effect of palmitate on glucose-induced AKT and PKC zeta/lambda phosphorylation and the stimulatory effect of palmitate on glucose-induced insulin secretion were not observed in the presence of fumonisin B1, all inhibitor of ceramide synthesis. Conclusions: These findings support the proposition that palmilate increases insulin release in the presence of 10 mM glucose by inhibiting PI3K activity through a mechanism that involves ceramide synthesis.