Z Li1, Y Zhu1, C Li1, Y Tang1, Z Jiang1, M Yang1, C-L Ni1, D Li1,2, L Chen3, W Niu4,5. 1. Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China. 2. Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin, 300070, China. 3. Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China. xfx22081@vip.163.com. 4. Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300070, China. wniu@tijmu.edu.cn. 5. Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin, 300070, China. wniu@tijmu.edu.cn.
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.
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, IRS1serines, and IKKα/β, but also the expression of IL-6, TNFα and IL-1β in C2C12-GLUT4myc cells. PA can reduce phosphorylation of IRS1tyrosine. 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 IRS1serine phosphorylation in PA-treated muscle cells.
Authors: André J Tremblay; Benoît Lamarche; Carolyn F Deacon; S John Weisnagel; Patrick Couture Journal: Metabolism Date: 2014-06-14 Impact factor: 8.694
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