Henkel, Janin and Gaertner, Daniela and Dorn, Christoph and Hellerbrand, Claus and Schanze, Nancy and Elz, Sheila R. and Pueschel, Gerhard P. (2011) Oncostatin M produced in Kupffer cells in response to PGE(2): possible contributor to hepatic insulin resistance and steatosis. LABORATORY INVESTIGATION, 91 (7). pp. 1107-1117. ISSN 0023-6837,
Full text not available from this repository. (Request a copy)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 (COX) products such as prostaglandin E-2 (PGE(2)). In a recent study, PGE(2) 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, PGE(2) in the liver might affect insulin resistance by modulating cytokine production in non-parenchymal cells. In accordance with this hypothesis, PGE(2) stimulated 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 suppressor of cytokine signaling 3 (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 PGE(2)-dependent feed-forward loop may be an additional, thus far unrecognized, mechanism contributing to hepatic insulin resistance and the development of NASH. Laboratory Investigation (2011) 91, 1107-1117; doi:10.1038/labinvest.2011.47; published online 25 April 2011
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NECROSIS-FACTOR-ALPHA; RAT HEPATOCYTES; PROSTAGLANDIN E-2; TNF-ALPHA; INTERLEUKIN-6; INHIBITION; MICE; DIET; EXPRESSION; OBESITY; cyclooxygenase; cytokine; hepatic steatosis; NASH; suppressor of cytokine signaling (SOCS); type II diabetes (T2DM) |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jun 2020 05:46 |
| Last Modified: | 09 Jun 2020 05:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20618 |
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