title: Effect of opioid mu-receptors activation on insulin signals damaged by tumor necrosis factor alpha in myoblast C2C12 cells.
abstract: In an attempt to develop a new target for handling of insulin resistance, we investigated the effect of opioid mu-receptor activation on insulin signals in differentiated myoblast C2C12 cells damaged by tumor necrosis factor-alpha (TNFalpha). A marked reduction of insulin-stimulated radioactive 2-deoxyglucose (2-DG) uptake was observed in TNFalpha (10 ng/ml for 1 h)-treated cells. Loperamide (10 micromol/l for 24 h) reversed the inhibition of insulin-stimulated 2-DG uptake by TNFalpha in a manner sensitive to blockade of opioid mu-receptors. Insulin signals damaged by TNFalpha were the impaired expressions of insulin receptor (IR), tyrosine autophosphorylation in IR, and insulin receptor substrate (IRS)-1 protein, as well as a decrease of IRS-1 tyrosine phosphorylation. Also, the signaling defects including an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation were observed. Loperamide (10 micromol/l for 24 h) reversed the TNFalpha-induced decrement of insulin signals at same concentration used to raise glucose uptake. In conclusion, activation of opioid mu-receptors may reverse the insulin signals damaged by inflammatory cytokine.
authors.affiliation: Department of Surgery, Mackay Memorial Hospital and Mackay College of Nursing and Technology, Taipei City, Taiwan, ROC.
authors.forename: Wen Ching
authors.initials: WC
authors.lastname: Ko
authors.forename: Tsang Pai
authors.initials: TP
authors.lastname: Liu
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.forename: Thing-Fong
authors.initials: TF
authors.lastname: Tzeng
authors.forename: I-Min
authors.initials: IM
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D008139:Loperamide / Q000494:pharmacology; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology* / Q000633:toxicity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D017450:Receptors, Opioid, mu; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D008139:Loperamide; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin