title: Carbamylated low-density lipoprotein attenuates glucose uptake via a nitric oxide-mediated pathway in rat L6 skeletal muscle cells.
abstract: Carbamylation is a cyanate-mediated posttranslational modification. We previously reported that carbamylated low-density lipoprotein (cLDL) increases reactive oxygen species and apoptosis via a lectin-like oxidized LDL receptor mediated pathway in human umbilical vein endothelial cells. A recent study reported an association between cLDL and type 2 diabetes mellitus (T2DM). In the current study, the effects of cLDL on glucose transport were explored in skeletal muscle cells. The effect of cLDL on glucose uptake, glucose transporter 4 (GLUT4) translocation, and signaling pathway were examined in cultured rat L6 muscle cells using 2-deoxyglucose uptake, immunofluorescence staining and western blot analysis. The quantity of nitric oxide (NO) was evaluated by the Griess reaction. The effect of native LDL (nLDL) from patients with chronic renal failure (CRF-nLDL) on glucose uptake was also determined. It was observed that cLDL significantly attenuated glucose uptake and GLUT4 translocation to the membrane, which was mediated via the increase in inducible nitric oxide synthase (iNOS)-induced NO production. Tyrosine nitration of the insulin receptor substrate-1 (IRS‑1) was increased. It was demonstrated that CRF-nLDL markedly reduced glucose uptake compared with nLDL from healthy subjects. Collectively, these findings indicate that cLDL, alone, attenuates glucose uptake via NO-mediated tyrosine nitration of IRS‑1 in L6 rat muscle cells and suggests the possibility that cLDL is involved in the pathogenesis of T2DM.
authors.affiliation: Department of Biochemistry and Pain Research Center, School of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Orthopedic Surgery, Keimyung University, Dongsan Medical Center, Daegu 700‑712, Republic of Korea.
authors.forename: Kyoung Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Dongsan Kidney Institute, Keimyung University, Dongsan Medical Center, Daegu 700‑712, Republic of Korea.
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry and Pain Research Center, School of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea.
authors.forename: Kyo-Cheol
authors.initials: KC
authors.lastname: Mun
authors.affiliation: Department of Biochemistry and Pain Research Center, School of Medicine, Keimyung University, Daegu 704‑701, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; C039916:carbamyl-LDL; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D005947:Glucose