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Promotion of ß-Cell Regeneration by Betacellulin in Ninety Percent-Pancreatectomized Rats

Department of Cell Biology (L.L., I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan 371-8512; and Department of Bioscience and Biotechnology (M.S., H.Y.), Faculty of Engineering, Okayama University, Okayama, Japan 700-8530

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

Betacellulin is thought to promote growth and differentiation of pancreatic ß-cells. We investigated the effect of betacellulin on regeneration of pancreatic ß-cells in 90%-pancreatectomized rats. Ninety percent pancreatectomy was performed in male Wistar rats and betacellulin (0.5 µg/g body weight) or saline was administered daily for 10 d starting immediately after pancreatectomy. In pancreatectomized rats, the morning-fed plasma glucose was significantly lower and the plasma insulin concentration was significantly higher in betacellulin-treated rats than those in control rats for up to 4 wk. Thirty days after pancreatectomy, a glucose tolerance test was performed. Betacellulin reduced the plasma glucose response to ip glucose loading. In control rats, the plasma insulin concentration was significantly lower and did not respond to glucose. In contrast, the plasma insulin concentration increased slightly but significantly in betacellulin-treated rats. Thirty days after pancreatectomy, the ß-cell mass was greater and the insulin content was significantly higher in betacellulin-treated rats than those in control rats. The numbers of islet cell-like cluster and bromodeoxy uridine/insulin double- positive cells in both islet cell-like cluster and islets were significantly higher in betacellulin-treated rats. These results indicate that administration of betacellulin improves glucose metabolism by promoting ß-cell regeneration in 90%-pancreatectomized rats.

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