Exendin-4 exerts its effects through the NGF/p75NTR system in diabetic mouse pancreas.
Glucagon-like peptide-1 (GLP-1) ameliorates the symptoms of diabetes through stimulation of insulin secretion. We have investigated the possible components of cellular mechanism triggered by exendin-4, a potent GLP-1 receptor agonist, in streptozotocin (STZ) induced diabetic mice pancreas. BALB/c male mice were divided into four groups for this investigation. The first group was given citrate buffer only, the second group was administered exendin-4 alone, the third group received STZ, and the fourth group was given both STZ and exendin-4. Exendin-4 (3 microg/kg) was administered by daily subcutaneous injection for 30 days after the animals were rendered diabetic by administration of STZ (200 mg/kg). With exendin-4 treatment on diabetic mice, the following results were noted: (i) exendin-4 suppressed the increase in plasma glucose and inhibited somatostatin expression induced by STZ, (ii) reduction of insulin prevalence was inhibited, while expression of p75 neurotrophin receptor (p75NTR), pancreatic nerve growth factor (NGF), and NGF-positive islet cell prevalence increased, (iii) there were no alterations in the severity of proliferated cell nuclear antigen positive or apoptotic beta cells in pancreatic islets, and (iv) pancreatic catalase, glutathione peroxidase, and superoxide dismutase activities significantly increased. In conclusion, these data suggest that exendin-4 might exert its actions through the NGF/p75NTR system and decrease somatostatin expression.
Gezginci-Oktayoglu
Selda
S
Department of Biology, Istanbul University, Faculty of Science, 34134-Vezneciler, Istanbul, Turkey. selgez@istanbul.edu.tr
Bolkent
Sehnaz
S
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D000077270:Exenatide; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D013004:Somatostatin / Q000096:biosynthesis; D013311:Streptozocin; D014688:Venoms / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D014688:Venoms; D013004:Somatostatin; D013311:Streptozocin; D000077270:Exenatide