Effect of opioid mu-receptors activation on insulin signals damaged by tumor necrosis factor alpha in myoblast C2C12 cells.
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.
Ko
Wen Ching
WC
Department of Surgery, Mackay Memorial Hospital and Mackay College of Nursing and Technology, Taipei City, Taiwan, ROC.
Liu
Tsang Pai
TP
Cheng
Juei-Tang
JT
Tzeng
Thing-Fong
TF
Liu
I-Min
IM
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
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