Abstract

Activin A and betacellulin (BTC) are thought to regulate differentiation of pancreatic β-cells during development and regeneration of β-cells in adults. In the present study, we used neonatal rats treated with streptozotocin (STZ) to investigate the effects of activin A and BTC on regeneration of pancreatic β-cells. One-day-old Sprague-Dawley rats were injected with STZ (85 μg/g) and then administered for 7 days with activin A and/or BTC. Treatment with activin A and BTC significantly reduced the plasma glucose concentration and the plasma glucose response to intraperitoneal glucose loading. The pancreatic insulin content and β-cell mass in rats treated with activin A and BTC were significantly increased compared with the control group on day 8 and at 2 months. Treatment with activin A and BTC significantly increased the DNA synthesis in preexisting β-cells, ductal cells, and δ-cells. The number of islet cell-like clusters (ICCs) and islets was significantly increased by treatment with activin A and BTC. In addition, the number of insulin/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells was significantly increased. These results indicate that, in neonatal STZ-treated rats, a combination of activin A and BTC promoted regeneration of pancreatic β-cells and improved glucose metabolism in adults.