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Diabetes 53:608-615, 2004
© 2004 by the American Diabetes Association, Inc.

Activin A and Betacellulin

Effect on Regeneration of Pancreatic ß-Cells in Neonatal Streptozotocin-Treated Rats

Lei Li1, Zhaohong Yi1, Masaharu Seno2, and Itaru Kojima1

1 Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
2 Department of Bioscience and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan

Activin A and betacellulin (BTC) are thought to regulate differentiation of pancreatic ß-cells during development and regeneration of ß-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 ß-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 ß-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 ß-cells, ductal cells, and {delta}-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 ß-cells and improved glucose metabolism in adults.

Address correspondence and reprint requests to Itaru Kojima, MD, Institute for Molecular & Cellular Regulation, Gunma University, Maebashi 371-8512, Japan. E-mail: ikojima{at}showa.gunma-u.ac.jp


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