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Ontogeny of Regeneration of β-Cells in the Neonatal Rat after Treatment with Streptozotocin

Sandra Thyssen, Edith Arany, D. J. Hill
2006 Endocrinology  
We induced a partial β−cell loss within the pancreas of neonatal rats using streptozotocin (STZ) to better characterize the mechanisms leading to β−cell regeneration postnatally. Rats were administered either STZ (70 mg/kg), or buffer alone, on postnatal day 4, and the endocrine pancreas examined between 4 and 40 days later. STZ-treated rats showed an approximate 60% loss of existing β−cells, and a moderate hyperglycemia less than 15mM glucose, with levels returning to near-control values after
more » ... ontrol values after 20 days. Within pre-existing islets there was increased cell proliferation in both insulin-and glucagon-positive cells at 8 days, and α−cell hyperplasia. This was associated with increased pancreatic content and circulating levels of glucagon. Pancreatic levels of glucagon-like polypeptide-1 (GLP-1) were increased 8 days post-STZ compared to controls and the GLP-1/glucagon ratio changed in favor of GLP-1. Administration of a GLP-1 receptor antagonist, GLP-1(9-39), resulted in a decreased recovery of β-cells following STZ, and a worse glucose tolerance. Atypical glucagon-positive cells were found within islets which co-localized Pdx-1 or Glut2. Pancreatic levels of insulin mRNA did not return to control values until 40 days post-STZ. Insulin-positive cells were found after 8 days that co-localized glucagon and GLP-1. The model shows that the pancreas of the young rat can rapidly regenerate a loss of β−cells, and that this is associated with a hyperplasia of α−cells with an altered phenotype of increased GLP-1 synthesis. The target cells of GLP-1 are likely to include immature β−cells that co-express proglucagon.
doi:10.1210/en.2005-0396 pmid:16484329 fatcat:c7dvgrfswbgizkvktkaw35gpjq