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

M.M. Thewissen, J. van de Gaar, A.T. den Boer, M.J.M. Marjet Munsters, E.E. Blaak, A.M. Duijvestijn

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: 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. METHODS: 25 study subjects were enrolled in the study. An oral glucose tolerance test (OGTT) was performed and, from fasting insulin and glucose, HOMA-IR was calculated. PBMC 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. RESULTS: Based on 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 NGT, IGM and T2DM subjects. Incubation with insulin did not induce Akt-phosphorylation in CD4+ and CD8+ T cells in NGT 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. CONCLUSIONS: 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 (c) 2013 John Wiley & Sons, Ltd.
Original languageEnglish
Pages (from-to)323-332
JournalDiabetes-metabolism Research and Reviews
Volume30
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

Cite this