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Diabetes 53:2596-2602, 2004
© 2004 by the American Diabetes Association, Inc.

Promotion of ß-Cell Differentiation by Conophylline in Fetal and Neonatal Rat Pancreas

Takeki Ogata1,2, Lei Li1, Satoko Yamada1, Yoritsuna Yamamoto2, Yuji Tanaka2, Izumi Takei3, Kazuo Umezawa4, and Itaru Kojima1

1 Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
2 Third Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan
3 Clinical Laboratory and Internal Medicine, Keio University School of Medicine, Tokyo, Japan
4 Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan

Conophylline is a vinca alkaloid extracted from the tropical plant Ervatamia microphylla and has been shown to induce differentiation of pancreatic AR42J cells. In the present study, we investigated the effect of conophylline on the differentiation of pancreatic precursor cells. In the rat pancreatic rudiment in organ culture, conophylline inhibited the formation of cystic structure and increased the number of insulin-positive cells. Conophylline also markedly increased the expression of mRNA for insulin and the number of pancreatic duodenal homeobox-1–positive cells. These effects of conophylline were similar to those of activin A. We also examined the effect of conophylline on neonatal rats treated with streptozotocin, a model of type 2 diabetes. Treatment with conophylline significantly reduced the plasma glucose concentration and improved glucose tolerance in response to glucose loading. The insulin content and the ß-cell mass at 2 months were significantly increased by conophylline. The number of islet-like cell clusters and pancreatic duodenal homeobox-1–positive ductal cells was greater in conophylline-treated rats. These results suggest that conophylline induces differentiation of pancreatic precursor cells and increases the formation of ß-cells.

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


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.