Abstract
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 effect of palmitate on insulin signaling
in 3T3-L1 adipocytes. We found that 1h treatment with 1 mmol/l palmitate had no effect
on insulin binding, tyrosine phosphorylation of insulin receptors, 185 kDa proteins
and Shc, and PI3 kinase activity in 3T3-L1 adipocytes. Then, the effects of palmitate
on MAP kinase activity and glucose uptake in fully differentiated 3T3-L1 adipocytes
were compared with those in poorly differentiated 3T3-L1 cells and in HIRc-B cells.
Palmitate treatment had no effect on MAP kinase activity in fully 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 that in control cells, but palmitate treatment caused
a rightward shift of the insulin-dose responsive curve for glucose uptake in HIRc-B
cells. Palmitate treatment did not significantly affect basal and insulin-stimulated
GLUT4 translocation. When the cells were treated with PD98059, a specific MEK inhibitor,
insulin-stimulated glucose uptake was not affected in 3T3-L1 adipocytes, while it
was almost completely inhibited in HIRc-B cells. These results suggest the primary
effect of palmitate on adipocytes may not involve insulin resistance of adipocytes
themselves.
Key words
Palmitate - 3T3-L1 Cell - HIRc-B Cell - Insulin Resistance - MAP Kinase
