Prolonged Treatment with Free Fatty Acids has Post Receptor Effect in Hepatic Insulin Resistance: Evidence that Fatty Acids, Oleate and Palmitate have Insignificant Effect on the Insulin Receptor Beta In Vivo and Ex Vivo Primary Hepatocytes

• Published in: Biochemistry Insights Vol. 2009; no. 2; p. BCI.S2850
• Main Authors: Ragheb, Rafik, Medhat, Amina M., Shanab, Gamila M.L., Seoudi, Dina M., Fantus, I.G.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publishing 12.06.2009; SAGE Publications; Sage Publications Ltd. (UK)
• Subjects: Amino acids; Diabetes therapy; Fatty acids; Fructose; Hamsters; Insulin resistance; Monosaccharides; Sugars; Tyrosine; free fatty acids; insulin signaling; hepatic insulin resistance; obesity
• ISSN: 1178-6264; 1178-6264
• DOI: 10.4137/BCI.S2850

Rafik Ragheb1,2,3,4,5, Amina M. Medhat1, Gamila M.L. Shanab1, Dina M. Seoudi1 and Fantus I.G.2,3,51University of Ain Shams, Department of Biochemistry, Faculty of Science, Cairo, Egypt. 2University Health Network, 3Mount Sinai Hospital, 4Hospital for Sick Children, 5University of Toronto, Toronto, Canada. AbstractIn the current study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor-beta subunit (IR-β), as well as the down stream target in PI3K pathway, total PKB/Akt as well as their phosphorylated forms. The assessment of FFAs treatment showed no direct and significant effect on the PI3K stimulation, specifically the IR-β in primary hepatic control cells treated with insulin. Cells treated with either oleate or palmitate (360 µM) showed no statistically significant values following insulin stimulation (P > 0.05). To further investigate the effect of both FFAs and high insulin (1 µg), we examined the effects of oleate and palmitate at 360 µM concentration on IR-β as well as PKB. There was no significant difference in the total protein levels and their phosphorylated forms in cells treated with or without oleate or plamitate. Interestingly, IR-β tyrosine phosphorylation showed a similar insignificant effect in vivo and ex vivo hepatic cells treated with oleate or palmitate in comparison to their controls in the fructose fed hamsters.