In the present study, we examined the effects of free fatty acids (FFAs) on insulin sensitivity and signaling cascades in the C2C12 skeletal muscle cell culture system. Our data clearly manifested that the inhibitory effects of PKC on insulin signaling may at least in part be explained by the serine/threonine phosphorylation of IRS-1. Both oleate and palmitate treatment were able to increase the Serine 307 phosphorylation of IRS-1. IRS-1 Serine 307 phosphorylation is inducible which causes the inhibition of IRS-1 tyrosine phosphorylation by either IκB-kinase (IKK) or c-jun N-terminal kinase (JNK) as seen in our proteomic kinases screen. Furthermore, our proteomic data have also manifested that the two FFAs activate the IKKα/β, the stress kinases S6 kinase p70 (p70SK), stress-activated protein kinase (SAPK), JNK, as well as p38 MAP kinase (p38MAPK). On the other hand, the antioxidant, Taurine at 10 mM concentrations was capable of reversing the oleate-induced insulin resistance in myocytes as manifested from the glucose uptake data. Our current data point out the importance of FFA-induced insulin resistance via multiple signaling mechanisms. KeywordsFree fatty acid (FFA); Insulin resistance (IR); Skeletal muscle cell (C2C12); Protein kinase C (PKC); Insulin receptor substrate-1 (IRS-1)

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In 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.

Background and Aim: Coptic Orthodox Christian (COC) diet is unique in that it regularly interchanges between an omnivorous to a vegetarian type of diet, through four fasting periods over the course of the ecclesiastical year. Several studies have described its dietary regulations, however, its possible involvement in health is lacking. The aim of the present study is to detect the metabolic changes during COC fasting. Subjects and Methods: Seventy two devout Orthodox Christian fasters, 25 of whom were diabetics and 40 matched controls, of whom 10 were diabetics, voluntarily participated in this study. A total of 240 blood samples were taken after at least 2 weeks before and during the different fasting periods. The fasting schedule was identified as either vegan (no sea food) or vegetarian (with sea food). Serum glucose (Glu), lipid profile, renal markers and hepatic enzymes, were measured and their within-subject biological variation was calculated. Results: The within-subject biological change due to fasting differed among subjects of the same group, gender and diet. Still, generally healthy subjects showed a decrease in Glu, triglycerides (TG) and TG/ high-density lipoprotein while the diabetics had a decline in blood urea nitrogen (BUN), BUN/ creatinine ratio and uric acid. Conclusion: The effect of fasting differs among subjects and we cannot generalize its effect on all people. The strong individuality observed supports the preferential use of within-subjects biological variations and the reference change values rather than population-based reference intervals.