Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines

Version 1 : Received: 14 December 2023 / Approved: 14 December 2023 / Online: 15 December 2023 (03:39:52 CET)

How to cite: Csurgyók, R.; Sütő, G.; Engelmann, P.; Wittmann, I.; Vas, T. Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines. Preprints 2023, 2023121123. https://doi.org/10.20944/preprints202312.1123.v1 Csurgyók, R.; Sütő, G.; Engelmann, P.; Wittmann, I.; Vas, T. Chronic Insulin Resistance and Changes of M1/M2 Polarization in Macrophages Due to Abnormal Tyrosines. Preprints 2023, 2023121123. https://doi.org/10.20944/preprints202312.1123.v1

Abstract

In obesity, white adipose tissue expresses inflammatory cytokines leading to insulin resistance. Non-physiological meta-tyrosine and ortho-tyrosine (meta-Tyr and ortho-Tyr), produced from phenylalanine by free radicals, may contribute to the development of insulin resistance. The resulting insulin resistance may have a significant impact on macrophage function. In this study we aim to investigate microscopically the effect of meta- and ortho-Tyr on insulin sensitivity and M1/M2 polarization of macrophages using Akt phosphorylation and the arginase 1/iNOS ratio. Macrophage cell lines were cultured in media containing para-, meta- or ortho-Tyr, 5 mmol/L or 25 mmol/L glucose (para25-Tyr group) and treated with insulin. Para25, meta- and ortho-Tyr increased pAkt levels and decreased the arginase 1/iNOS ratio in macrophages in the absence of insulin. In the case of physiological para-tyrosine treatment, insulin increased the amount of pAkt and decreased the arginase 1/iNOS ratio. Both meta- and ortho-Tyr treatment were able to abolish or reverse the insulin’s increasing effect on pAkt and the decreasing effect on arginase 1/iNOS ratio. Our results suggest that non-physiological tyrosine isomers may affect the insulin signaling of macrophages and influence their M1/M2 polarization.

Keywords

macrophages; oxidative stress; tyrosine isomers; pAkt, insulin resistance

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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