Identification and characterization of secretagogin promoter activity.
Secretagogin is a newly identified calcium-binding protein selectively expressed in neuroendocrine tissue and pancreatic beta-cells. The function of secretagogin is unknown, but it has been suggested in beta-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.
Skovhus
K V
KV
Steno Diabetes Center, Gentofte, Denmark.
Bergholdt
R
R
Erichsen
C
C
Sparre
T
T
Nerup
J
J
Karlsen
A E
AE
Pociot
F
F
D020121:5' Untranslated Regions / Q000235:genetics / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051381:Rats; D064046:Secretagogins; D024363:Transcription Initiation Site
D020121:5' Untranslated Regions; D002135:Calcium-Binding Proteins; D016207:Cytokines; C576556:SCGN protein, human; D064046:Secretagogins; D005947:Glucose