The role of clusterin on pancreatic beta cell regeneration after exendin-4 treatment in neonatal streptozotocin administrated rats.
We investigated the effects of exendin-4 (Ex4) treatment on expression of clusterin and β cell regeneration in the endocrine pancreas in neonatal streptozotocin (nSTZ) diabetic rats. Three groups were used: (1) n2-STZ group; on the second day after birth 100mg/kg STZ was given i.p. to two groups of newborn rats, (2) n2-STZ+Ex4 group; 3μg/kg/day Ex4 was given for 5 days starting on the third day, and (3) control group. In situ hybridization for mRNAs of insulin and clusterin, double immunostaining for insulin/clusterin and insulin/BrdU were carried out. Immunostaining for insulin, glucagon, somatostatin, clusterin, synaptophysin and pdx-1 was performed. In the n2-STZ+Ex4 group, BrdU/insulin and insulin/clusterin immunopositive cells were significantly increased in the islets of Langerhans in comparison to the other groups. The areas occupied by the insulin mRNA and peptide positive cells and also pdx-1 immunopositive cells were decreased in the n2-STZ diabetic group compared with the other groups. The clusterin mRNA and protein positive cells, and also the glucagon and somatostatin cells, were significantly increased in the islets of the n2-STZ and the n2-STZ+Ex4 groups compared with the control group. The results show that Ex4 treatment induces new beta cell clusters via up-regulation of clusterin, which might be effective on beta-cell proliferation and neogenesis.
Department of Medical Biology, Faculty of Cerrahpasa Medicine, Istanbul University, 34098 Cerrahpasa, Istanbul, Turkey. fkaya@istanbul.edu.tr
Fatma
F
Kaya-Dagistanli
Melek
M
Ozturk
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D051152:Clusterin / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D000077270:Exenatide; D015870:Gene Expression; D005934:Glucagon / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D017403:In Situ Hybridization; D050417:Insulin-Secreting Cells / Q000502:physiology*; D010455:Peptides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014688:Venoms / Q000627:therapeutic use*
D015415:Biomarkers; D001786:Blood Glucose; D051152:Clusterin; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D010455:Peptides; D012333:RNA, Messenger; D015534:Trans-Activators; D014688:Venoms; C084010:pancreatic and duodenal homeobox 1 protein; D005934:Glucagon; D000077270:Exenatide
Clusterin; Ex4; Exendin-4; GLP-1; Neonatal-STZ; PBS; Pancreatic islets; Pdx-1; Rat; Regeneration; SSC; STZ; beta cell; exendin-4; glucagon-like peptide-1; nCLU; nSTZ; neonatal streptozotocin; nuclear-clusterin; pancreatic duodenal homebox-1; phosphate-buffered-saline; sCLU; saline-sodium citrate; secreted-clusterin; streptozotocin; β cell