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Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

Title data

Manowsky, Julia ; Camargo, Rodolfo Gonzalez ; Kipp, Anna P. ; Henkel, Janin ; Püschel, Gerhard P.:
Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes.
In: American Journal of Physiology. Vol. 310 (1 June 2016) Issue 11 . - S. E938-E946.
ISSN 1522-1555
DOI: https://doi.org/10.1152/ajpendo.00427.2015

Abstract in another language

Overweight and obesity are associated with hyperinsulinemia, insulin resistance, and a low-grade inflammation. Although hyperinsulinemia is generally thought to result from an attempt of the β-cell to compensate for insulin resistance, there is evidence that hyperinsulinaemia itself may contribute to the development of insulin resistance and possibly the low-grade inflammation. To test this hypothesis, U937 macrophages were exposed to insulin. In these cells, insulin induced expression of the proinflammatory cytokines IL-1β, IL-8, CCL2, and OSM. The insulin-elicited induction of IL-1β was independent of the presence of endotoxin and most likely mediated by an insulin-dependent activation of NF-κB. Supernatants of the insulin-treated U937 macrophages rendered primary cultures of rat hepatocytes insulin resistant; they attenuated the insulin-dependent induction of glucokinase by 50%. The cytokines contained in the supernatants of insulin-treated U937 macrophages activated ERK1/2 and IKKβ, resulting in an inhibitory serine phosphorylation of the insulin receptor substrate. In addition, STAT3 was activated and SOCS3 induced, further contributing to the interruption of the insulin receptor signal chain in hepatocytes. These results indicate that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: cytokines; inflammation; insulin; macrophage; metabolic syndrome; type 2 diabetes
Institutions of the University: Faculties > Faculty of Life Sciences: Food, Nutrition and Health
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 570 Life sciences, biology
Date Deposited: 26 Apr 2021 12:30
Last Modified: 27 Apr 2021 11:43
URI: https://eref.uni-bayreuth.de/id/eprint/64440