tailieunhanh - Báo cáo khoa học: Insulin resistance in human adipocytes occurs downstream of IRS1 after surgical cell isolation but at the 1 level of phosphorylation of IRS1 in type 2 diabetes

Insulin resistance is a cardinal feature of type 2 diabetes and also a conse-quence of trauma such as surgery. Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incu-bation in 10% CO2 at 37 C 2 . 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 | ềFEBS Journal 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 Anna Danielsson1 Anita Ost1 Erika Lystedt1 Preben Kjolhede2 Johanna Gustavsson1 Fredrik H. Nystrom1 3 and Peter Stralfors1 1 Department of CellBiology and Diabetes Research Centre University of Linkoping Sweden 2 Department of Molecular and ClinicalMedicine Division of Obstetrics and Gynecology University of Linkoping Sweden 3 Department of Medicine and Care and the Diabetes Research Centre University of Linkoping Sweden Keywords glucose transport insulin receptor substrate MAP-kinase p38 protein kinase B Correspondence P. Stralfors Department of Cell Biology Faculty of Health Sciences SE58185 Linkoping Sweden Fax 46 13 224314 Tel 46 13 224315 E-mail Received 5 August 2004 accepted 17 September 2004 doi 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 CO2 at 37 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 .