Liraglutide ameliorates palmitate-induced insulin resistance through inhibiting the IRS-1 serine phosphorylation in mouse skeletal muscle cells.

Abstract

OBJECTIVE:

A reduction in insulin-stimulated glucose uptake in skeletal muscles is a characteristic of insulin resistance and type 2 diabetes mellitus (T2DM). The glucagon-like peptide (GLP)-1 agonist liraglutide can reduce blood glucose levels in individuals with T2DM. However, its effect on insulin-induced glucose metabolism in the skeletal muscle of insulin resistance is unknown. We investigated the effects and action mechanisms of liraglutide on insulin resistance (IR) in the skeletal muscle cells treatment with palmitic acid (PA).

METHODS:

The cell-surface GLUT4myc levels were determined by an antibody-coupled colorimetric assay. The phosphorylation levels of Akt, PI3K(p85α), AS160, IRS1, IKK, and JNK were determined by western blotting. The quantifications of mRNA levels of TNFα, IL-1β, and IL-6 were determined by real-time PCR. Analysis of variance was used for data analysis.

RESULTS:

PA elevated not only phosphorylation of JNK, IRS1 serines, and IKKα/β, but also the expression of IL-6, TNFα and IL-1β in C2C12-GLUT4myc cells. PA can reduce phosphorylation of IRS1 tyrosine. These effects of PA were reversed by liraglutide. In addition, liraglutide can reverse PA-decreased insulin-stimulated cell-surface GLUT4 levels, Akt, PI3K(p85α), and AS160 phosphorylation.

CONCLUSIONS:

Liraglutide can enhance insulin-induced GLUT4 translocation by inhibiting IRS1 serine phosphorylation in PA-treated muscle cells.

• Authors: Z Li, Y Zhu, C Li, Y Tang, Z Jiang, M Yang, C-L Ni, D Li, L Chen, W Niu
• Journal: Journal of endocrinological investigation (J Endocrinol Invest) Vol. 41 Issue 9 Pg. 1097-1102 (Sep 2018) ISSN: 1720-8386 [Electronic] Italy
• PMID: 29374854 (Publication Type: Journal Article)

Chemical References

• Glucose Transporter Type 4
• Hypoglycemic Agents
• Insulin Receptor Substrate Proteins
• Irs1 protein, mouse
• Palmitates
• Slc2a4 protein, mouse
• Liraglutide

Topics

• Animals
• Cell Line
• Glucose Transporter Type 4 (metabolism)
• Humans
• Hypoglycemic Agents (pharmacology)
• Insulin Receptor Substrate Proteins (antagonists & inhibitors, metabolism)
• Insulin Resistance (physiology)
• Liraglutide (pharmacology)
• Mice
• Muscle Fibers, Skeletal (drug effects, metabolism)
• Palmitates (toxicity)
• Phosphorylation (drug effects, physiology)