Palmitate activates insulin signaling pathway in pancreatic rat islets.
OBJECTIVE
To investigate the action of palmitate on insulin receptor (IR) signaling pathway in rat pancreatic islets. The following proteins were studied: IR substrate-1 and -2 (IRS1 and IRS2), phosphatidylinositol 3-kinase, extracellular signal-regulated protein kinase-1 and -2 (ERK1/2), and signal transducer and activator of transcription 3 (STAT3).


METHODS
Immunoblotting and immunoprecipitation assays were used to evaluate the phosphorylation states of IRS1 and IRS2 (tyrosine [Tyr]), ERK1/2 (threonine 202 [Thr202]/Tyr204), and STAT3 (serine [Ser727]).


RESULTS
The exposure of rat pancreatic islets to 0.1-mmol/L palmitate for up to 30 minutes produced a significant increase of Tyr phosphorylation in IRS2 but not in IRS1. The association of phosphatidylinositol 3-kinase with IRS2 was also upregulated by palmitate. Exposure to 5.6-mmol/L glucose caused a gradual decrease in ERK1/2 (Thr202/Tyr204) and STAT3 (serine [Ser727]) phosphorylations after 30-minute incubation. The addition of palmitate (0.1 mmol/L), associated with 5.6-mmol/L glucose, abolished these latter effects of glucose after 15-minute incubation.


CONCLUSIONS
Palmitate at physiological concentration associated with 5.6-mmol/L glucose activates IR signaling pathway in pancreatic beta cells.
Graciano
Maria Fernanda R
MF
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. mafe@icb.usp.br
Nogueira
Tatiane C A
TC
Carvalho
Carla R O
CR
Curi
Rui
R
Carpinelli
Angelo R
AR
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D005260:Female; D005947:Glucose / Q000494:pharmacology; D015151:Immunoblotting; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010168:Palmitates; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D005947:Glucose