Involvement of phosphatidylinositol-3 kinase/AKT/PKCzeta/lambda pathway in the effect of palmitate on glucose-induced insulin secretion.
OBJECTIVE
In the present study, a novel pathway by which palmitate 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 fumonisin B1 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 PKCzeta/lambda phosphorylation. Palmitate (0.1 mM) abolished glucose stimulation of AKT and PKCzeta/lambda phosphorylation possibly through PI3K inhibition because both LY294002 (50 microM) and wortmannin (100 nM) caused the same effect. The inhibitory effect of palmitate on glucose-induced AKT and PKCzeta/lambda phosphorylation and the stimulatory effect of palmitate on glucose-induced insulin secretion were not observed in the presence of fumonisin B1, an inhibitor of ceramide synthesis.


CONCLUSIONS
These findings support the proposition that palmitate increases insulin release in the presence of 10 mM glucose by inhibiting PI3K activity through a mechanism that involves ceramide synthesis.
Nogueira
Tatiane C A
TC
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil. tcanogueira@gmail.com
Anhê
Gabriel F
GF
Carvalho
Carla R O
CR
Curi
Rui
R
Bordin
Silvana
S
Carpinelli
Angelo R
AR
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002518:Ceramides / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D005260:Female; D037341:Fumonisins / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D015854:Up-Regulation; D000077191:Wortmannin; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
D000730:Androstadienes; D002518:Ceramides; D002867:Chromones; D037341:Fumonisins; D005947:Glucose; D007328:Insulin; D007527:Isoenzymes; D018832:Molecular Chaperones; D009025:Morpholines; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; D000099293:Protein Kinase C-lambda; C490392:Prkcz protein, rat; D000099221:Protein Kinase C zeta; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C056933:fumonisin B1