TY - JOUR
T1 - Activin A and Betacellulin
T2 - Effect on Regeneration of Pancreatic β-Cells in Neonatal Streptozotocin-Treated Rats
AU - Li, Lei
AU - Yi, Zhaohong
AU - Seno, Masaharu
AU - Kojima, Itaru
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1442276960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1442276960&partnerID=8YFLogxK
U2 - 10.2337/diabetes.53.3.608
DO - 10.2337/diabetes.53.3.608
M3 - Article
C2 - 14988244
AN - SCOPUS:1442276960
SN - 0012-1797
VL - 53
SP - 608
EP - 615
JO - Diabetes
JF - Diabetes
IS - 3
ER -
