Transcriptional Repressors Are Increased in Pancreatic Islets of Type 2 Diabetic Rats

To further clarify the mechanism of impaired insulin gene transcription in the diabetic state, we investigated the expression and function of the transcriptional repressor CREM (CRE modulator) in rat pancreatic islets. The CREM gene generates both transcriptional activators and repressors by alterna...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-12, Vol.253 (3), p.712-718
Main Authors: Inada, Akari, Yamada, Yuichiro, Someya, Yoshimichi, Kubota, Akira, Yasuda, Koichiro, Ihara, Yu, Kagimoto, Shinji, Kuroe, Akira, Tsuda, Kinsuke, Seino, Yutaka
Format: Article
Language:English
Subjects:
Animals
CREM
Cyclic AMP Response Element Modulator
Diabetes Mellitus, Type 2 - metabolism
DNA-Binding Proteins - metabolism
Gene Expression Regulation
GK rats
ICER
Insulin - biosynthesis
Insulin - genetics
insulin gene
Islets of Langerhans - metabolism
Male
novel isoform
Protein Isoforms
Rats
Rats, Mutant Strains
Rats, Wistar
Repressor Proteins - metabolism
RNA, Messenger - analysis
Testis - metabolism
Transcription, Genetic
type 2 diabetes
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Summary:To further clarify the mechanism of impaired insulin gene transcription in the diabetic state, we investigated the expression and function of the transcriptional repressor CREM (CRE modulator) in rat pancreatic islets. The CREM gene generates both transcriptional activators and repressors by alternative splicing and an intronic promoter. We isolated a novel alternatively spliced CREM isoform, CREM-17X, which efficiently represses insulin gene transcription, in addition to the three previously reported repressors. We also compared mRNA levels of insulin and the CREM repressors in pancreatic islets of Wistar and GK (Goto-Kakizaki) rats, the well-characterized spontaneous animal model of type 2 diabetes. The CREM repressor levels are increased, and the expression of insulin mRNA is decreased in GK rats, suggesting that increased CREM repressor expression in pancreatic islets could contribute to the decreased insulin gene transcription that results in impaired insulin secretion in type 2 diabetes.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.9833