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, cilt.32, sa.2, ss.223-231, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 32 Sayı: 2
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1016/j.peptides.2010.10.025
  • Dergi Adı: PEPTIDES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.223-231
  • Anahtar Kelimeler: Exendin-4, Hepatocyte, NGF, TrkA, p75(NTR), Oxidative stress, GLUCAGON-LIKE PEPTIDE-1, NERVE GROWTH-FACTOR, STELLATE CELLS EXPRESS, LIPID-PEROXIDATION, HEPATIC STEATOSIS, UNDERGO APOPTOSIS, OXIDATIVE STRESS, LIVER-INJURY, IN-VITRO, RECEPTOR
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.