Palmitate activates insulin signaling pathway in pancreatic rat islets

• Published in: Pancreas Vol. 38; no. 5; p. 578
• Main Authors: Graciano, Maria Fernanda R, Nogueira, Tatiane C A, Carvalho, Carla R O, Curi, Rui, Carpinelli, Angelo R
• Format: Journal Article
• Language: English
• Published: United States 01.07.2009
• Subjects: Animals; Caspase 3 - metabolism; Cell Line; Female; Glucose - pharmacology; Immunoblotting; Immunoprecipitation; In Vitro Techniques; Insulin Receptor Substrate Proteins - metabolism; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Macrophages - cytology; Macrophages - drug effects; Macrophages - enzymology; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Palmitates - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Rats; Receptor, Insulin - metabolism; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; Time Factors
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0b013e31819e65d1

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). 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]). 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. Palmitate at physiological concentration associated with 5.6-mmol/L glucose activates IR signaling pathway in pancreatic beta cells.