Insulin controls cell metabolism via metabolic signal transduction pathways and cell proliferation via mitogenic signal pathways. Metabolic signalling occurs through receptor-activated phosphorylation of insulin receptor substrate (IRS) proteins that subsequently activate phosphatidylinositide 3-kinase (PI3-kinase) to generate second messengers that produce increased phosphorylation and activation of protein kinase B ⁄ Akt (PKB). PKB appears to be central to downstream control of both glucose uptake and glycogen synthesis by insulin [1,2]. Although adipocytes are terminally differentiated cells that do not divide further, insulin has the potential for genomic control via a mitogenic signalling pathway. This may also be mediated by IRS; insulin activation of the G-protein Ras leads to phosphorylation and activation of mitogenactivated protein (MAP) kinases -extracellular signal-related kinase (ERK) 1 and 2 [3], and p38 [4,5] 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°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. 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 insulinstimulated tyrosine phosphorylation of insulin receptor, exhibited insulin resistance. These findings suggest a new approach in the study of surgeryinduced 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.Abbreviations ERK, extracellular signal-related kinase; GLUT4, insulin-sensitive glucose transporter-4; IRS, insulin receptor substrate; MAP, mitogenactivated protein; PKB, protein kinase B; PI3-kinase, phosphatidylinositide 3-kinase.

Background: Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome. Methods: Ten women diagnosed with PCOS were consecutively included (aged 21-39 years, average 30.2^1.9 years; body mass index 28.4 -42.5 kg/m