In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 1 ( 2001-01-02), p. 48-53
Abstract:
The regeneration of pancreatic islet β cells is important
for the prevention and cure of diabetes mellitus . We
have demonstrated that the administration of poly(ADP-ribose) synthetase/polymerase (PARP) inhibitors such as nicotinamide to 90%
depancreatized rats induces islet regeneration. From the regenerating islet-derived cDNA library, we have isolated Reg (regenerating gene) and demonstrated that Reg protein induces β-cell
replication via the Reg receptor and ameliorates experimental diabetes. However, the mechanism by which Reg gene is activated in
β cells has been elusive. In this study, we found that the combined addition of IL-6 and dexamethasone induced the expression of Reg gene in β cells and that PARP inhibitors enhanced
the expression. Reporter gene assays revealed that the −81 ≈ −70 region (TGCCCCTCCCAT) of the Reg gene promoter is a cis -element for the expression of Reg gene. Gel mobility shift assays showed that the active transcriptional
DNA/protein complex was formed by the stimulation with IL-6 and dexamethasone. Surprisingly, PARP bound to the cis -element and was involved in the active
transcriptional DNA/protein complex. The DNA/protein complex formation was inhibited depending on the autopoly(ADP-ribosyl)ation of
PARP in the complex. Thus, PARP inhibitors enhance the DNA/protein complex formation for Reg gene transcription and
stabilize the complex by inhibiting the autopoly(ADP-ribosyl)ation of PARP.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.98.1.48
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
