title: Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is linked to greater insulin resistance. Although HCV itself is a candidate for the development of insulin resistance, the effects of antiviral treatment on impaired glucose metabolism remain unclear. The aim of this study is to examine the effects of clearance of HCV on insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate (IRS)1/2, central molecules for insulin signaling.
  
  
  METHODS
  We analyzed 89 biopsy-proven patients with chronic HCV infection. Patients received interferon-alpha or interferon-alpha plus ribavirin for 6 months and were classified into three groups at 6 months after the conclusion of antiviral therapy according to their response to antiviral therapy: sustained responders (N = 29), relapsers (N = 12), and nonresponders (N = 48). Insulin resistance and beta-cell function were assessed by the homeostasis model assessment method (HOMA-IR and HOMA-%B, respectively). Hepatic expression of IRS1/2 was evaluated by immunoblotting and immunostaining in 14 sustained responders.
  
  
  RESULTS
  In nonresponders and relapsers, there were no significant changes in HOMA-IR and HOMA-%B values after antiviral therapy. On the other hand, in sustained responders, HOMA-IR values significantly decreased to 1.7 +/- 0.8 from 3.1 +/- 1.1 (P < 0.05) after antiviral therapy. Similarly, HOMA-%B values significantly decreased to 90.6 +/- 10.0 from 113.7 +/- 15.3 (P < 0.05). Immunoblotting showed a threefold increase in IRS1/2 expression after clearance of HCV. Immunostaining revealed that greater IRS1/2 expression was seen in hepatocytes.
  
  
  CONCLUSIONS
  We showed that clearance of HCV improves insulin resistance, beta-cell function, and hepatic IRS1/2 expression.
authors.affiliation: Department of Digestive Disease Information and Research, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ide
authors.forename: Eitaro
authors.initials: E
authors.lastname: Taniguchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hirano
authors.forename: Minoru
authors.initials: M
authors.lastname: Itou
authors.forename: Shuji
authors.initials: S
authors.lastname: Sumie
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nagao
authors.forename: Chikatoshi
authors.initials: C
authors.lastname: Yanagimoto
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hanada
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000096:biosynthesis*; D011379:Prognosis; D012367:RNA, Viral / Q000032:analysis; D011972:Receptor, Insulin / Q000096:biosynthesis; D019562:Viral Load
chemical_list: C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012367:RNA, Viral; D011972:Receptor, Insulin