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Transcriptional mechanism of suppression of insulin gene expression by AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in beta-cells.

Authors
Kim, JW; Cho, JH; Ko, SH; Park, HS; Ha, J; Song, KH; Son, HY; Kim, SS; Yoon, KH; Suh-Kim, H
Citation
Biochemical and biophysical research communications, 365(4):614-620, 2008
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
It is well known that the activation of AMP-activated protein kinase (AMPK) represses insulin gene expression and glucose-stimulated insulin secretion. However, how this effect is achieved and the effects of AMPK activation on glucolipotoxicity-induced beta-cell dysfunction have not been elucidated. We investigate whether BETA2 gene expression are involved in the AMPK-mediated regulation of insulin gene expression in normal and dysfunctional beta-cells. BETA2 gene expression and protein levels were significantly decreased by AICAR treatment and those were associated with the suppression of BETA2 promoter activity and DNA binding activity. These results demonstrate that the expressions of BETA2 and insulin gene are positively regulated by glucose and negatively by AMPK. Therefore, AMPK may function as a key molecule, which conveys extracellular metabolic signals into the cells and finely tunes expression of beta-cell specific transcription factors in response to glucose level.
MeSH terms
Aminoimidazole Carboxamide/administration & dosageAminoimidazole Carboxamide/analogs & derivatives*AnimalsCells, CulturedDose-Response Relationship, DrugDown-Regulation/drug effectsDown-Regulation/physiologyEnzyme Activation/drug effectsInsulin/metabolism*Insulin-Secreting Cells/drug effectsInsulin-Secreting Cells/metabolism*Protein Kinases/drug effects*Protein Kinases/metabolism*RatsRibonucleotides/administration & dosage*Signal Transduction/drug effectsSignal Transduction/physiology*Transcription, Genetic/drug effectsTranscription, Genetic/physiology*
DOI
10.1016/j.bbrc.2007.11.041
PMID
18035054
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Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
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