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Evidence for the Existence of CCK-Producing Cells in Rat Pancreatic Islets¹

Departments of Gastroenterology (K. Shim., K. Shir., S.W., N.H.) and Pathology (Y.K., M.K.), Tokyo Women’s Medical College, Tokyo 162, Japan; and Departments of Medicine (Y.S., T.-M.C., W.Y.C.) and Pediatrics (Y.D., R.F.), University of Rochester Medical Center, Rochester, New York 14642

Address all correspondence and requests for reprints to: Dr. Kyoko Shimizu, Tokyo Women’s Medical College, Department of Gastroenterology, 8-1 Kawada-cho, Shinjuku-Ku, Tokyo 162, Japan.

Background: Although the existence of cholecystokinin-like immunoreactivity (CCK-LI) in rat pancreas had been reported previously, it was never clearly demonstrated whether CCK is produced in rat pancreatic islets. Aims: The purpose of this study was to elucidate the source of the CCK-LI, the molecular properties of CCK, and the expression of the CCK gene in islet cells. Methods: Immunohistochemical studies of rat pancreas were carried out with different rabbit antisera against CCK-8 and CCK-related peptide including N-terminal CCK-33 (1–22) and gastrin-17, and colocalization with known islet hormones including insulin, glucagon, somatostatin, and pancreatic polypeptide was investigated. The major molecular form of CCK in the islets was determined by HPLC. RT-PCR and in situ hybridization were performed to demonstrate the presence of the CCK transcript in the pancreas. Results: CCK-LI was found in the center of the islets, colocalized with insulin in B cells. The major molecular form of CCK in the islets was CCK-8. A 350-nucleotide fragment of PCR-amplified CCK cDNA was detected in the islet as well as the duodenum by RT-PCR. In situ hybridization showed that CCK messenger RNA was located in a large portion of the islets, and this was consistent with the immunohistochemical findings. Conclusion: CCK messenger RNA and immunoreactivity are expressed in adult rat pancreatic islets, indicating that CCK-producing cells are present in adult rat islets.

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