Table of Contents
Hepatitis Research and Treatment
Volume 2013, Article ID 149247, 4 pages
http://dx.doi.org/10.1155/2013/149247
Research Article

Tryptophan-Kynurenine Metabolism and Insulin Resistance in Hepatitis C Patients

1Psychiatry and Inflammation Program, Department of Psychiatry, Tufts Medical Center, Tufts University, Boston, MA 02111, USA
2Department of Experimental and Clinical Pharmacology, Medical University, 20-090 Lublin, Poland
3Department of Toxicology, Institute of Rural Health, 20-090 Lublin, Poland
4Division of Gastroenterology/Hepatology, Tufts Medical Center, Tufts University, Boston, MA 02111, USA

Received 30 June 2013; Revised 5 August 2013; Accepted 7 August 2013

Academic Editor: Alessandro Antonelli

Copyright © 2013 G. F. Oxenkrug et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic hepatitis C virus (HCV) infection is associated with 50% incidence of insulin resistance (IR) that is fourfold higher than that in non-HCV population. IR impairs the outcome of antiviral treatment. The molecular mechanisms of IR in HCV are not entirely clear. Experimental and clinical data suggested that hepatitis C virus per se is diabetogenic. However, presence of HCV alone does not affect IR. It was proposed that IR is mediated by proinflammatory cytokines, mainly by TNF-alpha. TNF-alpha potentiates interferon-gamma-induced transcriptional activation of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan- (TRP-) kynurenine (KYN) metabolism. Upregulation of TRP-KYN metabolism was reported in HCV patients. KYN and some of its derivatives affect insulin signaling pathways. We hypothesized that upregulation of TRP-KYN metabolism might contribute to the development of IR in HCV. To check this suggestion, we evaluated serum concentrations of TRP and KYN and HOMA-IR and HOMA-beta in 60 chronic HCV patients considered for the treatment with IFN-alpha. KYN and TRP concentrations correlated with HOMA-IR and HOMA-beta scores. Our data suggest the involvement of KYN and its metabolites in the development of IR in HCV patients. TRP-KYN metabolism might be a new target for prevention and treatment of IR in HCV patients.