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

Ji Won Kim; Jae Hyoung Cho; Seung Hyun Ko; Heon seok Park; Joohun Ha; Ki Ho Song; Ho Young Son; Sung Soo Kim; Kun Ho Yoon; Haeyoung Suh-Kim

doi:10.1016/j.bbrc.2007.11.041

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

Ji Won Kim
, Jae Hyoung Cho
, Seung Hyun Ko
, Heon seok Park
, Joohun Ha
, Ki Ho Song
, Ho Young Son
, Sung Soo Kim
, Kun Ho Yoon
, Haeyoung Suh-Kim

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 β-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 β-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 β-cell specific transcription factors in response to glucose level.

Original language	English
Pages (from-to)	614-620
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	365
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2007.11.041
State	Published - 25 Jan 2008

Bibliographical note

Funding Information:
We thank Dr. In-Kyu Lee (Kyungpook National University) for expression vector for insulin promoter gene. We appreciated the expert technical assistance provided by Marie Rhee. This work was supported by Korea Research Foundation Grant, Republic of Korea; KRF-2004-041-E00155 and by a Grant (M103KV010008-07K2201-00810) to H.S.K. from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea.

Keywords

AMPK
ATCAR
BETA2
Insulin
Pdx-1

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10.1016/j.bbrc.2007.11.041

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Kim, J. W., Cho, J. H., Ko, S. H., Park, H. S., Ha, J., Song, K. H., Son, H. Y., Kim, S. S., Yoon, K. H., & Suh-Kim, H. (2008). Transcriptional mechanism of suppression of insulin gene expression by AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in β-cells. Biochemical and Biophysical Research Communications, 365(4), 614-620. https://doi.org/10.1016/j.bbrc.2007.11.041

@article{554431489cd34ee6914911ab9955ae7b,

title = "Transcriptional mechanism of suppression of insulin gene expression by AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in β-cells",

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 β-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 β-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 β-cell specific transcription factors in response to glucose level.",

keywords = "AMPK, ATCAR, BETA2, Insulin, Pdx-1",

author = "Kim, \{Ji Won\} and Cho, \{Jae Hyoung\} and Ko, \{Seung Hyun\} and Park, \{Heon seok\} and Joohun Ha and Song, \{Ki Ho\} and Son, \{Ho Young\} and Kim, \{Sung Soo\} and Yoon, \{Kun Ho\} and Haeyoung Suh-Kim",

note = "Funding Information: We thank Dr. In-Kyu Lee (Kyungpook National University) for expression vector for insulin promoter gene. We appreciated the expert technical assistance provided by Marie Rhee. This work was supported by Korea Research Foundation Grant, Republic of Korea; KRF-2004-041-E00155 and by a Grant (M103KV010008-07K2201-00810) to H.S.K. from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea.",

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month = jan,

day = "25",

doi = "10.1016/j.bbrc.2007.11.041",

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Kim, JW, Cho, JH, Ko, SH, Park, HS, Ha, J, Song, KH, Son, HY, Kim, SS, Yoon, KH & Suh-Kim, H 2008, 'Transcriptional mechanism of suppression of insulin gene expression by AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in β-cells', Biochemical and Biophysical Research Communications, vol. 365, no. 4, pp. 614-620. https://doi.org/10.1016/j.bbrc.2007.11.041

Transcriptional mechanism of suppression of insulin gene expression by AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in β-cells. / Kim, Ji Won; Cho, Jae Hyoung; Ko, Seung Hyun et al.
In: Biochemical and Biophysical Research Communications, Vol. 365, No. 4, 25.01.2008, p. 614-620.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Transcriptional mechanism of suppression of insulin gene expression by AMP-activated protein kinase activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in β-cells

AU - Kim, Ji Won

AU - Cho, Jae Hyoung

AU - Ko, Seung Hyun

AU - Park, Heon seok

AU - Ha, Joohun

AU - Song, Ki Ho

AU - Son, Ho Young

AU - Kim, Sung Soo

AU - Yoon, Kun Ho

AU - Suh-Kim, Haeyoung

N1 - Funding Information: We thank Dr. In-Kyu Lee (Kyungpook National University) for expression vector for insulin promoter gene. We appreciated the expert technical assistance provided by Marie Rhee. This work was supported by Korea Research Foundation Grant, Republic of Korea; KRF-2004-041-E00155 and by a Grant (M103KV010008-07K2201-00810) to H.S.K. from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea.

PY - 2008/1/25

Y1 - 2008/1/25

N2 - 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 β-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 β-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 β-cell specific transcription factors in response to glucose level.

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 β-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 β-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 β-cell specific transcription factors in response to glucose level.

KW - AMPK

KW - ATCAR

KW - BETA2

KW - Insulin

KW - Pdx-1

UR - https://www.scopus.com/pages/publications/37049033241

U2 - 10.1016/j.bbrc.2007.11.041

DO - 10.1016/j.bbrc.2007.11.041

M3 - Article

C2 - 18035054

AN - SCOPUS:37049033241

SN - 0006-291X

VL - 365

SP - 614

EP - 620

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

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