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A molecular inventory of human pancreatic islets: sequence analysis of 1000 cDNA clones
Insights
Researchers created a gene database from human islet cells to study diabetes. This collection of expressed sequence tags offers new genetic insights into islet function and diabetes mellitus.
Area of Science:
- Endocrinology
- Genomics
- Molecular Biology
Background:
- The islets of Langerhans regulate glucose homeostasis via insulin and glucagon secretion.
- Beta-cell loss or dysfunction causes diabetes mellitus.
- Understanding islet gene expression is crucial for diabetes research.
Purpose of the Study:
- To create a comprehensive database of genes expressed in human pancreatic islets.
- To identify novel genes involved in islet function and diabetes.
- To facilitate genetic and molecular studies of diabetes mellitus.
Main Methods:
- Isolation and partial sequencing of 1,000 cDNA clones from a human pancreatic islet library.
- Database searches to identify known genes and expressed sequence tags.
- Analysis of novel sequences not found in existing databases.
Main Results:
- Sequencing yielded 280 kilobases of human islet gene data.
- 397 cDNAs represented known human genes or homologs.
- 545 cDNAs were novel sequences, with <10% exocrine contamination.
Conclusions:
- The human islet cDNA collection is a valuable resource for diabetes genetic studies.
- This database aids molecular investigations into normal and diabetic islet function.
- Identified novel genes may offer new therapeutic targets for diabetes.
Abstract:
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.
