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Identification and Characterization of Secretagogin Promoter Activity
Author(s) -
Skovhus K. V.,
Bergholdt R.,
Erichsen C.,
Sparre T.,
Nerup J.,
Karlsen A. E.,
Pociot F.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2006.01854.x
Subject(s) - pancreatic islets , biology , promoter , microbiology and biotechnology , endocrinology , gene , medicine , islet , diabetes mellitus , gene expression , genetics
Secretagogin is a newly identified calcium‐binding protein selectively expressed in neuroendocrine tissue and pancreatic β ‐cells. The function of secretagogin is unknown, but it has been suggested in β ‐cells to influence calcium‐influx, insulin secretion and proliferation, and has been observed downregulated in diabetes‐prone BB rat islets exposed to cytokines. In the present study, we identified and characterized promoter activity of a human 1498 bp sequence upstream the transcription start site. The promoter sequence showed subtle but significant regulation by glucose within the normo‐physiological range. Glucose also led to changes in expression of secretagogin protein in INS‐1e cells, but not in primary cells from non‐diabetes‐prone Wistar Furth rats. No effects of cytokines neither on promoter activity nor protein expression were observed. The promoter region was furthermore screened by direct sequencing, and 11 polymorphisms were identified. Genotyping in a large homogenous Type 1 diabetes (T1D) family collection did not reveal association with T1D.