Abstract
Elevated plasma levels of free fatty acids (FFA) can produce insulin resistance in
skeletal muscle tissue and liver and, together with alterations in β-cell function,
this has been referred to as lipotoxicity. This study explores the effects of FFAs
on insulin action in rat adipocytes. Cells were incubated 4 or 24 h with or without
an unsaturated FFA, oleate or a saturated FFA, palmitate (0.6 and 1.5 mM, respectively).
After the culture period, cells were washed and insulin effects on glucose uptake
and lipolysis as well as cellular content of insulin signaling proteins (IRS-1, PI3-kinase,
PKB and phosphorylated PKB) and the insulin regulated glucose transporter GLUT4 were
measured. No significant differences were found in basal or insulin-stimulated glucose
uptake in FFA-treated cells compared to control cells, regardless of fatty acid concentration
or incubation period. Moreover, there were no significant alterations in the expression
of IRS-1, PI3-kinase, PKB and GLUT4 following FFA exposure. Insulin’s ability to stimulate
PKB phosphorylation was also left intact. Nor did we find any alterations following
FFA exposure in basal or cAMP-stimulated lipolysis or in the ability of insulin to
inhibit lipolysis. The results indicate that oleate or palmitate does not directly
influence insulin action to stimulate glucose uptake and inhibit lipolysis in rat
fat cells. Thus, lipotoxicity does not seem to occur in the fat tissue itself.
Key words
Glucose transport - Rat adipocytes - Oleate - Palmitate
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Dr. J. W. Eriksson
Department of Medicine · Umeå University Hospital
SE-901 85 Umeå · Sweden
Phone: +46(90)-7851853
Fax: +46(90)137633
Email: jan.eriksson@medicin.umu.se