Insulin resistance, defective insulin receptor substrate 2-associated phosphatidylinositol-3' kinase activation, and impaired atypical protein kinase C (zeta/lambda) activation in myotubes from obese patients with impaired glucose tolerance

Détails

ID Serval
serval:BIB_3B8BC3F9A861
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Insulin resistance, defective insulin receptor substrate 2-associated phosphatidylinositol-3' kinase activation, and impaired atypical protein kinase C (zeta/lambda) activation in myotubes from obese patients with impaired glucose tolerance
Périodique
Diabetes
Auteur(s)
Vollenweider  P., Menard  B., Nicod  P.
ISSN
0012-1797 (Print)
Statut éditorial
Publié
Date de publication
04/2002
Volume
51
Numéro
4
Pages
1052-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Résumé
Impaired glucose tolerance (IGT) is characterized by insulin resistance. Recently, defects in the insulin-signaling cascade have been implicated in the pathogenesis of insulin resistance. To study insulin signaling in IGT, we used human skeletal muscle cells in primary culture from patients with IGT and control subjects. In these cultured myotubes, we assessed insulin-induced 2-deoxyglucose uptake and early steps of the metabolic insulin-signaling cascade. Myotubes in culture from patients with IGT had insulin-induced glucose uptake that was roughly 30-50% less than that from control subjects. This insulin resistance was associated with impaired insulin receptor substrate (IRS)-2-associated phosphatidylinositol 3' (PI3) kinase activation and IRS-2 tyrosine phosphorylation as well as significantly decreased protein kinase C (PKC)-zeta/lambda activation in response to insulin. IRS-1- associated PI3 kinase activation and insulin receptor autophosphorylation were comparable in the two groups. Protein expression levels for the insulin receptor, IRS-1, IRS-2, the p85 regulatory subunit of PI3 kinase, Akt, PKC-zeta/lambda, GLUT1, and GLUT4 were also similar in the two groups. In conclusion, myotubes from patients with IGT have impaired insulin-induced glucose uptake. This is associated with impaired IRS-2-associated PI3 kinase activation and PKC-zeta/lambda activation. Our results suggest that these defects may contribute to insulin resistance in IGT patients.
Mots-clé
1-Phosphatidylinositol 3-Kinase/*metabolism Adipose Tissue/anatomy & histology Adult Biological Transport/drug effects Blood Glucose Blood Pressure Body Mass Index Cells, Cultured Deoxyglucose/pharmacokinetics Enzyme Activation Glucose Intolerance/metabolism/*physiopathology Glucose Tolerance Test Humans Insulin/*pharmacology Intracellular Signaling Peptides and Proteins Middle Aged Muscle, Skeletal/drug effects/*metabolism Obesity/*metabolism/physiopathology Phosphoproteins/*metabolism Phosphorylation Phosphotyrosine/metabolism Protein Kinase C/*metabolism Receptor, Insulin/*metabolism Reference Values
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:00
Dernière modification de la notice
20/08/2019 14:31
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