Exendin-4 improves hepatocyte injury by decreasing proliferation through blocking NGF/TrkA in diabetic mice.
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 (3μg/kg) was administered by subcutaneous injection daily for 30 days after the animals were rendered diabetic by administration of STZ (200mg/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.
Istanbul University, Department of Biology, 34134 Vezneciler, Istanbul, Turkey.
Selda
S
Gezginci-Oktayoglu
Ozlem
O
Sacan
Refiye
R
Yanardag
Ayse
A
Karatug
Sehnaz
S
Bolkent
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D000077270:Exenatide; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D020800:Receptor, Nerve Growth Factor; D014688:Venoms; D013311:Streptozocin; D020932:Nerve Growth Factor; D000077270:Exenatide; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D020917:Receptor, trkA; C505409:Casp3 protein, mouse; D053148:Caspase 3; D005978:Glutathione