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
Details
Serval ID
serval:BIB_3B8BC3F9A861
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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
Journal
Diabetes
ISSN
0012-1797 (Print)
Publication state
Published
Issued date
04/2002
Volume
51
Number
4
Pages
1052-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Research Support, Non-U.S. Gov't --- Old month value: Apr
Abstract
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.
Keywords
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
Yes
Create date
25/01/2008 15:00
Last modification date
20/08/2019 14:31