PMID- 18035054
OWN - NLM
STAT- MEDLINE
DCOM- 20080110
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 365
IP  - 4
DP  - 2008 Jan 25
TI  - Transcriptional mechanism of suppression of insulin gene expression by 
      AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside 
      (AICAR) in beta-cells.
PG  - 614-20
AB  - 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.
FAU - Kim, Ji-Won
AU  - Kim JW
AD  - Department of Endocrinology and Metabolism, The Catholic University of Korea, 
      505, Ban-po-Dong, Seocho-Gu, Seoul 137-090, Republic of Korea.
FAU - Cho, Jae-Hyoung
AU  - Cho JH
FAU - Ko, Seung-Hyun
AU  - Ko SH
FAU - Park, Heon-Seok
AU  - Park HS
FAU - Ha, Joohun
AU  - Ha J
FAU - Song, Ki-Ho
AU  - Song KH
FAU - Son, Ho-Young
AU  - Son HY
FAU - Kim, Sung-Soo
AU  - Kim SS
FAU - Yoon, Kun-Ho
AU  - Yoon KH
FAU - Suh-Kim, Haeyoung
AU  - Suh-Kim H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071121
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Insulin)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Aminoimidazole Carboxamide/administration & dosage/*analogs & derivatives
MH  - Animals
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects/physiology
MH  - Enzyme Activation/drug effects
MH  - Insulin/*metabolism
MH  - Insulin-Secreting Cells/drug effects/*metabolism
MH  - Protein Kinases/*drug effects/*metabolism
MH  - Rats
MH  - Ribonucleotides/*administration & dosage
MH  - Signal Transduction/drug effects/*physiology
MH  - Transcription, Genetic/drug effects/*physiology
EDAT- 2007/11/24 09:00
MHDA- 2008/01/11 09:00
CRDT- 2007/11/24 09:00
PHST- 2007/10/25 00:00 [received]
PHST- 2007/11/04 00:00 [accepted]
PHST- 2007/11/24 09:00 [pubmed]
PHST- 2008/01/11 09:00 [medline]
PHST- 2007/11/24 09:00 [entrez]
AID - S0006-291X(07)02399-6 [pii]
AID - 10.1016/j.bbrc.2007.11.041 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 Jan 25;365(4):614-20. doi: 
      10.1016/j.bbrc.2007.11.041. Epub 2007 Nov 21.