Endothelial cells are highly heterogeneous at the level of cytokine‐induced insulin resistance

Abstract

The endothelial wall plays a crucial role in various diseases as it serves as the barrier between circulatory system and organ tissue. Inflammation-driven insulin resistance and subsequent endothelial dysfunction represent a pathomechanism in cardiovascular diseases such as atherosclerosis and myocardial infarction. It was recently suggested that insulin resistance also contributes to the pathogenesis of psoriasis, a chronic inflammatory disease of the skin. However, it is not clear whether similar mechanisms at the endothelium contribute to the disease. In this study, we ask which endothelial cells are most suitable to address this question. We investigated the insulin response of four cell types (primary cells and cell lines) representing different vascular beds (micro- and macrovascular cells) in the presence of different pro-inflammatory cytokines. All four cell types used responded well to insulin; however, the ability to become resistant to insulin due to an inflammatory stimulus by cytokines involved in psoriasis (e.g. IL-1β, IL-12, IL-17, IL-23 and TNF-α) was very heterogeneous and could not be attributed to the differential expression of the cognate cytokine receptors. We conclude that this disparity is due to the different origins and properties of the endothelial cells used. Thus, endothelial cells should be carefully selected for the purpose of the respective study, particularly when it comes to analysing the pathogenesis of a disease and the search of new molecular targets for innovative therapies.

Studying the effect of systemic and biological drugs on intima‐media thickness in patients suffering from moderate and severe psoriasis

“…Further, our research has allowed us to observe a reduction in insulin and glucose levels due to IL‐12/23 blocking. Both interleukins are tightly connected to the development of peripheral resistance to insulin, and IL‐12/23 blockade has been studied as a possible treatment for patients suffering from type‐I diabetes …”

Exercise training reduces insulin resistance in postmyocardial infarction rats

“…; Woth et al. ), causing insulin receptor injury and its downstream signaling pathways suppression to lead to IR (Ohta et al. ; Fukushima et al.…”

Breakfast partly restores the anti-inflammatory function of high-density lipoproteins from patients with type 2 diabetes mellitus

“…This may partly explain why we observed no difference in the effect of patient and control HDL on HCAEC. Our data suggest that the effects of HDL vary between macro- and microvascular endothelial cells, but also among macrovascular endothelial cells derived from different organs, underlining the known heterogeneity in the structure and function of endothelial cells [ 43 ].…”