A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones.

The islets of Langerhans play a central role in glucose homeostasis by secreting the polypeptide hormones insulin and glucagon. They are comprised primarily of four endocrine cell types: insulin-secreting beta-cells which represent about 70% of the cells in the islet along with smaller number of cells secreting glucagon, somatostatin and pancreatic polypeptide. Diabetes mellitus results from the specific loss or dysfunction of the beta-cells. Because of the central role of the islets of Langerhans in the regulation of glucose homeostasis, we are preparing a database of genes expressed in this tissue. One thousand cDNA clones randomly isolated from a human pancreatic islet library were partially sequenced yielding 280 kilobases of sequence. Database searches indicated that 397 of the cDNAs represented known human genes or human homologs of genes identified in other species and a further 58 sequences corresponded to expressed sequence tags identified in other tissues or cells (contamination by exocrine pancreatic tissue was estimated to be less than 10%). 545 of the cDNAs were not related to any other sequences in the databases. The islet cDNA collection provides a unique source of genes for genetic studies of diabetes as well as for molecular studies of islet function in normal and diabetic states.