Tryptophan-Kynurenine Metabolism and Insulin Resistance in Hepatitis C Patients

Abstract EN

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.