Exendin-4 improves hepatocyte injury by decreasing proliferation through blocking NGF/TrkA in diabetic mice

Gezginci-Oktayoglu S. , Sacan O. , Yanardag R. , Karatug A. , Bolkent S.

PEPTIDES, vol.32, no.2, pp.223-231, 2011 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 32 Issue: 2
  • Publication Date: 2011
  • Doi Number: 10.1016/j.peptides.2010.10.025
  • Title of Journal : PEPTIDES
  • Page Numbers: pp.223-231


The hepatocytes express nerve growth factor (NGF) and its high affinity receptor tyrosine kinase A (TrkA). However, the link between NGF/TrkA system and hepatocyte proliferation in diabetic animals and the effects of exendin-4, a glucagon like peptide-1 (GLP-1) receptor agonist, on this system are not known. BALB/c male mice were divided into four groups. The first group was given citrate buffer only, the second group was administered exendin-4 alone, the third group received streptozotocin (STZ), and the fourth group was given both STZ and exendin-4. Exendin-4 (3 mu g/kg) was administered by subcutaneous injection daily for 30 days after the animals were rendered diabetic by administration of STZ (200 mg/kg). With treatment of exendin-4 to the diabetic mice the following results were noted (i) NGF, TrkA and proliferating cell nuclear antigen positive hepatocytes were decreased; (ii) p75 neurotrophin receptor and caspase-3 positive hepatocyte could not be detected; (iii) liver alanine transaminase and aspartate transaminase activities, lipid peroxidation, protein carbonyl and myeloperoxidase levels were decreased; (iv) liver catalase, superoxide dismutase, glutathione peroxidase activities and glutathione levels were increased. These data suggest that exendin-4 might exerts its anti-proliferative action through blocking NGF/TrkA system and stimulating oxidative defense system in liver of diabetic mice. (C) 2010 Elsevier Inc. All rights reserved.