PMID- 29374854 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20181231 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 41 IP - 9 DP - 2018 Sep TI - Liraglutide ameliorates palmitate-induced insulin resistance through inhibiting the IRS-1 serine phosphorylation in mouse skeletal muscle cells. PG - 1097-1102 LID - 10.1007/s40618-018-0836-x [doi] AB - 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(p85alpha), AS160, IRS1, IKK, and JNK were determined by western blotting. The quantifications of mRNA levels of TNFalpha, IL-1beta, 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 IKKalpha/beta, but also the expression of IL-6, TNFalpha and IL-1beta 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(p85alpha), and AS160 phosphorylation. CONCLUSIONS: Liraglutide can enhance insulin-induced GLUT4 translocation by inhibiting IRS1 serine phosphorylation in PA-treated muscle cells. FAU - Li, Z AU - Li Z AD - 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. FAU - Zhu, Y AU - Zhu Y AD - 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. FAU - Li, C AU - Li C AD - 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. FAU - Tang, Y AU - Tang Y AD - 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. FAU - Jiang, Z AU - Jiang Z AD - 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. FAU - Yang, M AU - Yang M AD - 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. FAU - Ni, C-L AU - Ni CL AD - 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. FAU - Li, D AU - Li D AD - 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. AD - Key Laboratory of Immuno Microenvironment and Disease of the Educational Ministry of China, Department of Immunology, Tianjin Medical University, Tianjin, 300070, China. FAU - Chen, L AU - Chen L AD - 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. FAU - Niu, W AU - Niu W AD - 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. AD - 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. LA - eng GR - 81670731/National Natural Science Foundation of China/ GR - 14JCYBJC26200/Natural Science Foundation of Tianjin City/ GR - 15JCZDJC35500/Tianjin Municipal Science and Technology Commission/ GR - 15KG102/Tianjin Health and Family Planning Commission/ GR - 15ZXHLSY00460/Tianjin Municipal Science and Technology Commission/ PT - Journal Article DEP - 20180127 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Glucose Transporter Type 4) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 0 (Palmitates) RN - 0 (Slc2a4 protein, mouse) RN - 839I73S42A (Liraglutide) SB - IM MH - Animals MH - Cell Line MH - Glucose Transporter Type 4/metabolism MH - Humans MH - Hypoglycemic Agents/*pharmacology MH - Insulin Receptor Substrate Proteins/antagonists & inhibitors/*metabolism MH - Insulin Resistance/*physiology MH - Liraglutide/*pharmacology MH - Mice MH - Muscle Fibers, Skeletal/drug effects/*metabolism MH - Palmitates/*toxicity MH - Phosphorylation/drug effects/physiology OTO - NOTNLM OT - IRS1 serine phosphorylation OT - Liraglutide OT - Skeletal muscle insulin resistance EDAT- 2018/01/29 06:00 MHDA- 2019/01/01 06:00 CRDT- 2018/01/29 06:00 PHST- 2017/07/11 00:00 [received] PHST- 2018/01/14 00:00 [accepted] PHST- 2018/01/29 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/01/29 06:00 [entrez] AID - 10.1007/s40618-018-0836-x [pii] AID - 10.1007/s40618-018-0836-x [doi] PST - ppublish SO - J Endocrinol Invest. 2018 Sep;41(9):1097-1102. doi: 10.1007/s40618-018-0836-x. Epub 2018 Jan 27.