Somatostatin (SRIF) is a tetradecapeptide which was originally isolated from the hypothalamus. Its complete amino acid sequence is known and much has been learned about its biologic activity. In addition to being an inhibitor of growth hormone release, SRIF has been found to inhibit the release of a number of other hormones including insulin and glucagon, suggesting a possible role for SRIF in the etiology of diabetes mellitus. SRIF has been localized by immunologic means in cells or cell processes in extrahypothalamic sites including the cerebral cortex, dorsal root ganglia, mucosa of the gastrointestinal tract, thyroid parafollicular cells and the D cells of pancreatic islets. Until recently, there was no evidence to indicate that SRIF is actually synthesized in extrahypothalamic sites. Using the isolated pancreatic islets of anglerfish incubated in vitro, we have been able to demonstrate not only that radioactively labeled amino acids become incoroprated into SRIF from these islets, but that SRIF biosynthesis apparently involves the participation of a larger, precursor (prosomatostatin). The goals of the proposed research are to further confirm and extend this finding by using biochemical techniques to identify, isolate and characterize prosomatostatin from anglerfish islets and to elucidate the process of precursor-to-product conversion. An additional goal is to determine the size of the primary gene product in SRIF biosynthesis by translating isolated islet mRNA in a cell-free (wheat germ) system. The cellfree translation product would then be isolated by immunoprecipitation and used for further characterization of the precursor-product relationship and metabolic conversion process. The results obtained from these studies should provide an informational basis for further investigation into the mechanisms controlling somatostatin synthesis and release which could, in turn lead to clarification of the possible role of SRIF in the etiology of diabetes mellitus or other pathologic states in which abnormal release of somatostatin may be a factor.
| Roth, W W; Mackin, R B; Spiess, J et al. (1991) Primary structure and tissue distribution of anglerfish carboxypeptidase H. Mol Cell Endocrinol 78:171-8 |
| Mackin, R B; Noe, B D; Spiess, J (1991) The anglerfish somatostatin-28-generating propeptide converting enzyme is an aspartyl protease. Endocrinology 129:1951-7 |
| Mackin, R B; Noe, B D; Spiess, J (1991) Identification of a somatostatin-14-generating propeptide converting enzyme as a member of the kex2/furin/PC family. Endocrinology 129:2263-5 |
