Suppression of free fatty acid-induced insulin resistance by phytopolyphenols in C2C12 mouse skeletal muscle cells
Journal
Journal of Agricultural and Food Chemistry
Journal Volume
60
Journal Issue
4
Pages
1059-1066
Date Issued
2012
Author(s)
Abstract
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. ? 2011 American Chemical Society.
Subjects
insulin resistance; phytopolyphenols; skeletal muscle cells; type 2 diabetes
Other Subjects
Acetyl-CoA carboxylase; Akt phosphorylation; AMP-activated protein kinase; Curcumin; Energy regulation; Epicatechin; Epigallocatechin gallate; Free fatty acid; Gallate; Glucose uptake; Insulin receptor substrate-1; Insulin resistance; Insulin-stimulated glucose; MAPK signaling; P38 MAPK; phytopolyphenols; Plasma levels; Polyphenols; Protein kinase C; Skeletal muscle; Skeletal muscle cells; Type 2 diabetes mellitus; Type-2 diabetes; Chemical activation; Electrocardiography; Energy policy; Enzyme activity; Fatty acids; Glucose; Insulin; Mammals; Muscle; Phenols; Phosphorylation; Cells; catechin; curcumin; drug derivative; epigallocatechin gallate; fatty acid; insulin receptor substrate; palmitic acid; phorbol 13 acetate 12 myristate; polyphenol; protein kinase C; serine; animal; article; cell line; drug effect; enzyme activation; insulin resistance; metabolism; mouse; phosphorylation; signal transduction; skeletal muscle; Animals; Catechin; Cell Line; Curcumin; Enzyme Activation; Fatty Acids, Nonesterified; Insulin Receptor Substrate Proteins; Insulin Resistance; Mice; Muscle, Skeletal; Palmitic Acid; Phosphorylation; Polyphenols; Protein Kinase C; Serine; Signal Transduction; Tetradecanoylphorbol Acetate
Type
journal article