Palmitate modulates the early steps of insulin signalling pathway in pancreatic islets.
Insulin stimulates its own secretion and synthesis by pancreatic beta-cells. Although the exact molecular mechanism involved is unknown, changes in beta-cell insulin signalling have been recognized as a potential link between insulin resistance and its impaired release, as observed in non-insulin-dependent diabetes. However, insulin resistance is also associated with elevated plasma levels of free fatty acids (FFA) that are well known modulators of insulin secretion by pancreatic islets. This information led us to investigate the effect of FFA on insulin receptor signalling in pancreatic islets. Exposure of pancreatic islets to palmitate caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor and pp185. This is the first evidence that short exposure of these cells to 100 microM palmitate activates the early steps of insulin receptor signalling. 2-Bromopalmitate, a carnitine palmitoyl-CoA transferase-1 inhibitor, did not affect the effect of the fatty acid. Cerulenin, an acylation inhibitor, abolished the palmitate effect on protein levels and phosphorylation of insulin receptor. This result supports the proposition that protein acylation may be an important mechanism by which palmitate exerts its modulating effect on the intracellular insulin signalling pathway in rat pancreatic islets.
Haber
Esther P
EP
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes 1524, Butantã, Brazil.
Hirabara
Sandro M
SM
Gomes
André D
AD
Curi
Rui
R
Carpinelli
Angelo R
AR
Carvalho
Carla R O
CR
D000818:Animals; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin; D010168:Palmitates; C022776:2-bromopalmitate; D019308:Palmitic Acid; D014443:Tyrosine; D011972:Receptor, Insulin