Article

Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the level of phosphorylation of IRS1 in type 2 diabetes.

Department of Cell Biology and Diabetes Research Centre, University of Linköping, Sweden.
FEBS Journal (impact factor: 3.79). 02/2005; 272(1):141-51. DOI:10.1111/j.1432-1033.2004.04396.x
Source: PubMed

ABSTRACT Insulin resistance is a cardinal feature of type 2 diabetes and also a consequence of trauma such as surgery. Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incubation in 10% CO(2) at 37 degrees C. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. MAP-kinases ERK1/2 and p38 were strongly phosphorylated after surgery, but was dephosphorylated during reversal of insulin resistance. Phosphorylation of MAP-kinase was not caused by collagenase treatment during cell isolation and was present also in tissue pieces that were not subjected to cell isolation procedures. The insulin resistance directly after surgery and cell isolation was different from insulin resistance of type 2 diabetes; adipocytes from patients with type 2 diabetes remained insulin resistant after overnight incubation. IRS1, PKB, and downstream metabolic effects, but not insulin-stimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. These findings suggest a new approach in the study of surgery-induced insulin resistance and indicate that human adipocytes should recover after surgical procedures for analysis of insulin signalling. Moreover, we pinpoint the signalling dysregulation in type 2 diabetes to be the insulin-stimulated phosphorylation of IRS1 in human adipocytes.

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Keywords

37 degrees C. Tyrosine phosphorylation
 
cell isolation procedures
 
collagenase treatment
 
downstream metabolic effects
 
downstream metabolic effects exhibited insulin resistance
 
exhibited insulin resistance
 
human adipocytes
 
incubation
 
insulin receptor substrate
 
Insulin resistance
 
insulin resistant
 
insulin signalling
 
insulin-stimulated phosphorylation
 
insulin-stimulated tyrosine phosphorylation
 
MAP-kinases ERK1/2
 
PKB
 
protein kinase B
 
surgery-induced insulin resistance
 
surgical procedures
 
type 2 diabetes