Abstract | BACKGROUND: MATERIALS AND METHODS: Rat islets were incubated at normoxic or hypoxic conditions and with or without hydrogen peroxide and a nitric oxide donor. Insulin mRNA was determined by Northern hybridization. Islet homogenates were used for electrophoretic mobility shift assay with an RNA- oligonucleotide, corresponding to the pyrimidine-rich sequence of the 3'-UTR of rat insulin I mRNA. The expression of reporter gene mRNA, in islets transfected with reporter gene constructs containing the wild-type or mutated insulin mRNA pyrimidine-rich sequences, was measured by semiquantitive RT-PCR. RESULTS: CONCLUSIONS: The complete understanding of different diabetic conditions requires the elucidation of mechanisms that control insulin gene expression. Our data show that hypoxia may increase insulin mRNA levels by promoting the binding of PTB to the insulin mRNA 3'-UTR. Hydrogen peroxide abolishes the hypoxic effect indicating involvement of reactive oxygen species and/or the redox potential in the oxygen-signaling pathway.
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Authors | Linda Tillmar, Nils Welsh |
Journal | Molecular medicine (Cambridge, Mass.)
(Mol Med)
Vol. 8
Issue 5
Pg. 263-72
(May 2002)
ISSN: 1076-1551 [Print] England |
PMID | 12359957
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3' Untranslated Regions
- Insulin
- RNA, Messenger
- Polypyrimidine Tract-Binding Protein
- Nitric Oxide
- Hydrogen Peroxide
- Oxygen
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Topics |
- 3' Untranslated Regions
(metabolism)
- Animals
- Hydrogen Peroxide
(metabolism)
- Hypoxia
(metabolism)
- Insulin
(biosynthesis, genetics)
- Islets of Langerhans
(metabolism)
- Nitric Oxide
(metabolism)
- Oxygen
(metabolism)
- Partial Pressure
- Polypyrimidine Tract-Binding Protein
(metabolism)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Sprague-Dawley
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