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Henkel, Janin ; Gärtner, Daniela ; Dorn, Christoph ; Hellerbrand, Claus ; Schanze, Nancy ; Elz, Sheila R. ; Püschel, Gerhard P.:
Oncostatin M produced in Kupffer cells in response to PGE2 : possible contributor to hepatic insulin resistance and steatosis.
In: Laboratory Investigation.
Bd. 91
(2011)
Heft 7
.
- S. 1107-1117.
ISSN 1530-0307
DOI: https://doi.org/10.1038/labinvest.2011.47
Abstract
Hepatic insulin resistance is a major contributor to hyperglycemia in metabolic syndrome and type II diabetes. It is caused in part by the low-grade inflammation that accompanies both diseases, leading to elevated local and circulating levels of cytokines and cyclooxygenase products such as prostaglandin E2 (PGE2). In a recent study, PGE2 produced in Kupffer cells attenuated insulin-dependent glucose utilization by interrupting the intracellular signal chain downstream of the insulin receptor in hepatocytes. In addition to directly affecting insulin signaling in hepatocytes, PGE2 in the liver might affect insulin resistance by modulating cytokine production in non-parenchymal cells. In accordance with this hypothesis, PGE2 stimulated in the current study oncostatin M (OSM) production by Kupffer cells. OSM in turn attenuated insulin-dependent Akt-activation and, as a downstream target, glucokinase induction in hepatocytes, most likely by inducing SOCS3. In addition, it inhibited the expression of key enzymes of hepatic lipid metabolism. COX 2 and OSM mRNA were induced early in the course of the development of non-alcoholic steatohepatitis (NASH) in mice. Thus, induction of OSM production in Kupffer cells by an autocrine PGE2-dependent feed-forward loop may be an additional, thus far unrecognized, mechanism contributing to hepatic insulin resistance and the development of NASH.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Institutionen der Universität: | Fakultäten > Fakultät für Lebenswissenschaften: Lebensmittel, Ernährung und Gesundheit Fakultäten Fakultäten > Fakultät für Lebenswissenschaften: Lebensmittel, Ernährung und Gesundheit > Lehrstuhl Biochemie der Ernährung > Lehrstuhl Biochemie der Ernährung - Univ.-Prof. Dr. Janin Henkel-Oberländer Fakultäten > Fakultät für Lebenswissenschaften: Lebensmittel, Ernährung und Gesundheit > Lehrstuhl Biochemie der Ernährung |
| Titel an der UBT entstanden: | Nein |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
| Eingestellt am: | 26 Apr 2021 11:24 |
| Letzte Änderung: | 17 Mai 2021 06:53 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/64430 |