Differential effects of palmitate on glucose uptake in rat-1 fibroblasts and 3T3-L1 adipocytes

Non-esterified fatty acids are thought to be one of the causes for insulin resistance. However, the molecular mechanism of fatty acid-induced insulin resistance is not clearly known. In this study, we first examined the effec t of palmitate on insulin signaling in 3T3-L1 adipocytes. We found that Ih treatment with 1 mmol/l palmitate had no effect on insulin binding, tyrosin e phosphorylation of insulin receptors, 185 kDa proteins and Shc, and P13 k inase activity in 3T3-L1 adipocytes. Then, the effects of palmitate on MAP kinase activity and glucose uptake in fully differentiated 3T3-L1 adipocyte s were compared with those in poorly differentiated 3T3-L1 cells and in HIR c-B cells. Palmitate treatment had no effect on MAP kinase activity in full y differentiated 3T3-L1 adipocytes, while it inhibited MAP kinase in poorly differentiated 3T3-L1 cells and HIRc-B cells. Glucose transport in 3T3-L1 adipocytes treated with palmitate for 1 h, 4 h and 16 h was higher than tha t in control cells, but palmitate treatment caused a rightward shift of the insulin-dose responsive curve for glucose uptake in HIRc-B cells. Palmitat e treatment did not significantly affect basal and insulin-stimulated GLUT4 translocation. When the cells were treated with PD98059, a specific MEK in hibitor, insulin-stimulated glucose uptake was not affected in 3T3-L1 adipo cytes, while it was almost completely inhibited in HIRc-B cells. These resu lts suggest the primary effect of palmitate on adipocytes may not involve i nsulin resistance of adipocytes themselves.