Monocytes, but not T cells, respond to insulin with Akt(S473) phosphorylation independent of the donor glucometabolic state. Issue 4 (May 2014)

• Record Type: Journal Article
• Authors: Thewissen, M. M.; van de, J.; den, A. Th.; Munsters, M. J.; Blaak, E. E.; Duijvestijn, A.
• Is Part Of: Diabetes/metabolism research and reviews. Volume 30:Issue 4(2014:May)
• Page Start: 323
• Page End: 332
• Publication Date: 2014-05
• Subjects: Diabetes -- Periodicals; Metabolism -- Periodicals; 616.642
• DOI: 10.1002/dmrr.2498
• Languages: English
• ISSNs: 1520-7552

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="dmrr2498-sec-0001" sec-type="section"> <title>Background</title> <p>Obesity is associated with insulin resistance and chronic low‐grade inflammation. Insulin has been described to have anti‐inflammatory effects in immune cells. Therefore, insulin resistance in immune cells can be expected to have important consequences for immune function. Here, we investigate whether freshly isolated monocytes and T cells, isolated from study subjects with a normal or disturbed glucometabolic state, respond to insulin with phosphorylation of Akt, a key molecule in the insulin signalling pathway.</p> </sec> <sec id="dmrr2498-sec-0002" sec-type="section"> <title>Methods</title> <p>A total of 25 study subjects were enrolled in the study. An oral glucose tolerance test (OGTT) was performed, and from fasting insulin and glucose, the homeostasis model assessment of insulin resistance (HOMA‐IR) index was calculated. Peripheral blood mononuclear cells were isolated from heparinized blood and phenotypically characterized by flow cytometry. Basal and insulin‐induced fractions of pAkt(S473)‐positive monocytes and T cells were determined by Phosflow.</p> </sec> <sec id="dmrr2498-sec-0003" sec-type="section"> <title>Results</title> <p>On the basis of the OGTT, 11 subjects were classified as normal glucose tolerant (NGT), 9 had an impaired glucose metabolism (IGM) and 5 had type 2 diabetes (T2DM). The fraction of pAkt(S473)positive‐T cells and monocytes, in the absence of insulin, was low in all subjects. Incubation with insulin did not induce Akt phosphorylation in CD4<sup>+</sup> and CD8<sup>+</sup> T cells in normal subjects. However, in the monocyte fraction, an insulin‐dose‐dependent increase of the pAkt(S473)positive‐cell fraction was observed. This response did not differ between NGT, IGM and T2DM and was not correlated with HOMA‐IR.</p> </sec> <sec id="dmrr2498-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In this study, we show that freshly isolated monocytes, but not T cells, are insulin‐sensitive cells and that this insulin sensitivity of monocytes is not negatively affected by the glucometabolic state of the donor. Copyright © 2013 John Wiley & Sons, Ltd.</p> </sec> </abstract>