It was reported that increased plasma levels of
free fatty acids (FFAs) are associated with profound
insulin resistance in skeletal muscle and may also play a critical role in the
insulin resistance of
obesity and
type 2 diabetes mellitus. Skeletal muscle is the major site for
insulin-stimulated
glucose uptake and is involved in energy regulation and homeostasis. In this study, we used 12-O-tetradecanoylphorbol 13-acetate (TPA), a
protein kinase C (PKC) activator, and
palmitate to induce
insulin resistance in C2C12 mouse skeletal muscle cells. Our data show that
epigallocatechin gallate (EGCG) and
curcumin treatment reduce
insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation, and
curcumin is more potent to increase Akt phosphorylation in TPA induction. Moreover, we found that after 5 h of
palmitate incubation,
epicatechin gallate (ECG) can suppress IRS-1 Ser307 phosphorylation and significantly promote Akt, ERK1/2,
p38 MAPK, and
AMP-activated protein kinase activation. With a longer incubation with
palmitate, IRS-1 exhibited a dramatic depletion, and treatment with EGCG, ECG, and
curcumin could reverse IRS-1 expression, Akt phosphorylation, and MAPK signaling cascade activation and improve
glucose uptake in C2C12 skeletal muscle cells, especially ECG and
curcumin. In addition, treatment with these
polyphenols can suppress
acetyl-CoA carboxylase activation, but only EGCG could inhibit
lipid accumulation in the intracellular site. These findings may suggest that
curcumin shows the best capacity to improve FFA-induced
insulin resistance than the other two, and ECG was more effective than EGCG in attenuating
insulin resistance.