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The stimulation of glucose transport, lipogenesis and glycogen synthase activity were analyzed in 3T3-L1 adipocyte cell lines to determine the effects of oxidant stress on adipocyte insulin resistance. Prolonged exposure of 3T3-L1 adipocyte cell lines to glucose oxidase increased the uptake of basal 2-deoxyglucose and enhanced basal lipoxygenase activity. However, basal lipoxygenase activity was significantly reduced by insulin stimulation in a dose-dependent manner.

A study using the L6 line of skeletal muscle cells was conducted to determine the effect of the iron chelators deferoxamine and bipyridyl on glucose transport and the expression of the GLUT-1 transmembrane glycoprotein in cultured muscle cells. The results show that L6 muscle cells responded to the reduction of iron availability due to iron chelators by enhancing GLUT-1 expression, which increased glucose transport. Furthermore, muscle cells adapted to reduced iron availability without losing their normal sensitivity to insulin.

MAPKs and inhibitory-kappaB kinase (IKK) were suggested to link various conditions thought to develop in adipose tissue in obesity (oxidative, endoplasmic reticulum stress, inflammation) with insulin resistance. Yet whether in obesity these kinases are affected in a fat-depot-differential manner is unknown. We assessed the expression and phosphorylation of these kinases in paired omental and abdominal-sc fat biopsies from 48 severely obese women (body mass index > 32 kg/m(2)). Protein and mRNAs of p38MAPK, ERK, c-Jun kinase-1, and IKKbeta were increased 1.5-2.5-fold in omental vs. sc fat. The phosphorylated (activated) forms of these kinases were also increased to similar magnitudes as the total expression. However, phosphorylation of insulin receptor substrate-1 on Ser312 (equivalent of murine Ser307) was not increased in omental, compared with sc, fat. Consistently, fat tissue fragments stimulated with insulin demonstrated that tyrosine phosphorylation and signal transduction to Akt/protein kinase B in omental fat was not inferior to that observable in sc fat. Comparison with lean women (body mass index 23.2 +/- 2.9 kg/m(2)) revealed similar ERK2 and IKKbeta expression and phosphorylation in both fat depots. However, as compared with lean controls, obese women exhibited 480 and 270% higher amount of the phosphorylated forms of p38MAPK and c-Jun kinase, respectively, in omental, but not sc, fat, and this expression level correlated with clinical parameters of glycemia and insulin sensitivity. Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity, potentially contributing to differential roles of omental and sc fat in the pathophysiology of obesity.