Down-regulation of hepatic AMP-activated protein kinase and up-regulation of CREB coactivator CRTC2 for gluconeogenesis under calorie-restricted conditions at a young age

Lucas Siqueira Trindade, Seong Joon Park, Toshimitsu Komatsu, Haruyoshi Yamaza, Hiroko Hayashi, Ryoichi Mori, Takuya Chiba, Isao Shimokawa, Kazunao Kuramoto

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

AMP-activated protein kinase (AMPK) is a key molecule that controls energy homeostasis at cellular and whole body levels. Calorie restriction (CR) may exhibit the anti-aging effect through modulation of AMPK activity. We investigated the hepatic AMPK pathways for gluconeogenesis (the transducer of regulated cyclic adenosine monophosphate response element-binding protein (CREB) 2; CRTC2) and cell growth (mammalian target of rapamycin, mTOR). Male F344 rats at 2.5 months (mo) and 18 mo of age were subjected to 4-mo-long 30% CR; control rats were fed ad libitum (AL) throughout the experiment. Rats were killed 15 min after saline or glucose injection to evaluate activation of signal molecules under transient hyperglycemic and subsequent hyperinsulinemic conditions. Western blot analyses demonstrated a modest reduction of threonine-172-phosphorylated (p)-AMPKα levels and an increment of nuclear CRTC2 in the young CR group as compared with the age-matched AL group. We also confirmed the increased binding of CRTC2 and CREB and up-regulation of gluconeogenic genes (PGC-1α and PEPCK) in the CR group. However, there was no CR-specific alteration in total or phosphorylated mTOR levels. The results suggest down-regulation of hepatic AMPK activity by CR for metabolic adaptation that promotes gluconeogenesis. The effect of CR on mTOR remains elusive.

元の言語英語
ページ(範囲)85-92
ページ数8
ジャーナルActa Medica Nagasakiensia
55
発行部数2
DOI
出版物ステータス出版済み - 1 1 2011
外部発表Yes

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AMP-Activated Protein Kinases
Gluconeogenesis
Up-Regulation
Down-Regulation
Sirolimus
Liver
CREB-Binding Protein
Inbred F344 Rats
Response Elements
Threonine
Transducers
Cyclic AMP
Homeostasis
Western Blotting
Glucose
Injections
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

Down-regulation of hepatic AMP-activated protein kinase and up-regulation of CREB coactivator CRTC2 for gluconeogenesis under calorie-restricted conditions at a young age. / Trindade, Lucas Siqueira; Park, Seong Joon; Komatsu, Toshimitsu; Yamaza, Haruyoshi; Hayashi, Hiroko; Mori, Ryoichi; Chiba, Takuya; Shimokawa, Isao; Kuramoto, Kazunao.

:: Acta Medica Nagasakiensia, 巻 55, 番号 2, 01.01.2011, p. 85-92.

研究成果: ジャーナルへの寄稿記事

Trindade, Lucas Siqueira ; Park, Seong Joon ; Komatsu, Toshimitsu ; Yamaza, Haruyoshi ; Hayashi, Hiroko ; Mori, Ryoichi ; Chiba, Takuya ; Shimokawa, Isao ; Kuramoto, Kazunao. / Down-regulation of hepatic AMP-activated protein kinase and up-regulation of CREB coactivator CRTC2 for gluconeogenesis under calorie-restricted conditions at a young age. :: Acta Medica Nagasakiensia. 2011 ; 巻 55, 番号 2. pp. 85-92.
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abstract = "AMP-activated protein kinase (AMPK) is a key molecule that controls energy homeostasis at cellular and whole body levels. Calorie restriction (CR) may exhibit the anti-aging effect through modulation of AMPK activity. We investigated the hepatic AMPK pathways for gluconeogenesis (the transducer of regulated cyclic adenosine monophosphate response element-binding protein (CREB) 2; CRTC2) and cell growth (mammalian target of rapamycin, mTOR). Male F344 rats at 2.5 months (mo) and 18 mo of age were subjected to 4-mo-long 30{\%} CR; control rats were fed ad libitum (AL) throughout the experiment. Rats were killed 15 min after saline or glucose injection to evaluate activation of signal molecules under transient hyperglycemic and subsequent hyperinsulinemic conditions. Western blot analyses demonstrated a modest reduction of threonine-172-phosphorylated (p)-AMPKα levels and an increment of nuclear CRTC2 in the young CR group as compared with the age-matched AL group. We also confirmed the increased binding of CRTC2 and CREB and up-regulation of gluconeogenic genes (PGC-1α and PEPCK) in the CR group. However, there was no CR-specific alteration in total or phosphorylated mTOR levels. The results suggest down-regulation of hepatic AMPK activity by CR for metabolic adaptation that promotes gluconeogenesis. The effect of CR on mTOR remains elusive.",
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AU - Trindade, Lucas Siqueira

AU - Park, Seong Joon

AU - Komatsu, Toshimitsu

AU - Yamaza, Haruyoshi

AU - Hayashi, Hiroko

AU - Mori, Ryoichi

AU - Chiba, Takuya

AU - Shimokawa, Isao

AU - Kuramoto, Kazunao

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