Evidence for the existence of CCK-producing cells in rat pancreatic islets

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.