Does the mechanism responsible for TNF-mediated insulin resistance involve the proteasome?
Recent studies have demonstrated that in many pathological states there is an overproduction of tumour necrosis factor-alpha (TNF). Interestingly, TNF also seems to be responsible for the insulin resistance associated with these pathological states, since decreases the tyrosine kinase activity of the insulin receptor. Our group has demonstrated that TNF is able to activate the proteasome-mediated ubiquitin-dependent proteolysis. Since this proteolytic system is involved in the control of receptor-associated tyrosine kinase activity (i.e. insulin receptor), it is postulated here that the mechanism of TNF-induced insulin resistance is mediated by the activation of the proteasomic, ubiquitin-dependent proteolysis.
Pallarés-Trujillo
J
J
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Carbó
N
N
López-Soriano
F J
FJ
Argilés
J M
JM
D003546:Cysteine Endopeptidases / Q000502:physiology*; D004789:Enzyme Activation; D006868:Hydrolysis; D007328:Insulin / Q000378:metabolism / Q000502:physiology; D007333:Insulin Resistance; D009097:Multienzyme Complexes / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014452:Ubiquitins / Q000502:physiology
D007328:Insulin; D009097:Multienzyme Complexes; D014409:Tumor Necrosis Factor-alpha; D014452:Ubiquitins; D011972:Receptor, Insulin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex