Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks

Kentaro Kawata, Atsushi Hatano, Katsuyuki Yugi, Takanori Sano, Masashi Fujii, Yoko Tomizawa, Toshiya Kokaji, Kaori Y. Tanaka, Shinsuke Uda, Y. Suzuki, Masaki Matsumoto, Keiichi Nakayama, Kaori Saitoh, Keiko Kato, Ayano Ueno, Maki Ohishi, Akiyoshi Hirayama, Tomoyoshi Soga, Shinya Kuroda

研究成果: ジャーナルへの寄稿記事

抄録

The concentrations of insulin selectively regulate multiple cellular functions. To understand how insulin concentrations are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells using transcriptomic data, western blotting analysis of signaling proteins, and metabolomic data. By integrating sensitivity into the trans-omic network, we identified the selective trans-omic networks stimulated by high and low doses of insulin, denoted as induced and basal insulin signals, respectively. The induced insulin signal was selectively transmitted through the pathway involving Erk to an increase in the expression of immediate-early and upregulated genes, whereas the basal insulin signal was selectively transmitted through a pathway involving Akt and an increase of Foxo phosphorylation and a reduction of downregulated gene expression. We validated the selective trans-omic network in vivo by analysis of the insulin-clamped rat liver. This integrated analysis enabled molecular insight into how liver cells interpret physiological insulin signals to regulate cellular functions.
元の言語英語
ページ(範囲)212-229
ジャーナルiScience
7
早期オンライン日9 10 2018
出版物ステータス出版済み - 2018

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Gene Regulatory Networks
Metabolic Networks and Pathways
Insulin
Immediate-Early Genes
Metabolomics
Liver
Hepatocellular Carcinoma
Down-Regulation
Western Blotting
Phosphorylation
Gene Expression

これを引用

Kawata, K., Hatano, A., Yugi, K., Sano, T., Fujii, M., Tomizawa, Y., ... Kuroda, S. (2018). Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks. iScience, 7, 212-229.

Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks. / Kawata, Kentaro; Hatano, Atsushi; Yugi, Katsuyuki; Sano, Takanori; Fujii, Masashi; Tomizawa, Yoko; Kokaji, Toshiya; Tanaka, Kaori Y.; Uda, Shinsuke; Suzuki, Y.; Matsumoto, Masaki; Nakayama, Keiichi; Saitoh, Kaori; Kato, Keiko; Ueno, Ayano; Ohishi, Maki; Hirayama, Akiyoshi; Soga, Tomoyoshi; Kuroda, Shinya.

:: iScience, 巻 7, 2018, p. 212-229.

研究成果: ジャーナルへの寄稿記事

Kawata, K, Hatano, A, Yugi, K, Sano, T, Fujii, M, Tomizawa, Y, Kokaji, T, Tanaka, KY, Uda, S, Suzuki, Y, Matsumoto, M, Nakayama, K, Saitoh, K, Kato, K, Ueno, A, Ohishi, M, Hirayama, A, Soga, T & Kuroda, S 2018, 'Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks', iScience, 巻. 7, pp. 212-229.
Kawata, Kentaro ; Hatano, Atsushi ; Yugi, Katsuyuki ; Sano, Takanori ; Fujii, Masashi ; Tomizawa, Yoko ; Kokaji, Toshiya ; Tanaka, Kaori Y. ; Uda, Shinsuke ; Suzuki, Y. ; Matsumoto, Masaki ; Nakayama, Keiichi ; Saitoh, Kaori ; Kato, Keiko ; Ueno, Ayano ; Ohishi, Maki ; Hirayama, Akiyoshi ; Soga, Tomoyoshi ; Kuroda, Shinya. / Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks. :: iScience. 2018 ; 巻 7. pp. 212-229.
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abstract = "The concentrations of insulin selectively regulate multiple cellular functions. To understand how insulin concentrations are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells using transcriptomic data, western blotting analysis of signaling proteins, and metabolomic data. By integrating sensitivity into the trans-omic network, we identified the selective trans-omic networks stimulated by high and low doses of insulin, denoted as induced and basal insulin signals, respectively. The induced insulin signal was selectively transmitted through the pathway involving Erk to an increase in the expression of immediate-early and upregulated genes, whereas the basal insulin signal was selectively transmitted through a pathway involving Akt and an increase of Foxo phosphorylation and a reduction of downregulated gene expression. We validated the selective trans-omic network in vivo by analysis of the insulin-clamped rat liver. This integrated analysis enabled molecular insight into how liver cells interpret physiological insulin signals to regulate cellular functions.",
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AU - Kawata, Kentaro

AU - Hatano, Atsushi

AU - Yugi, Katsuyuki

AU - Sano, Takanori

AU - Fujii, Masashi

AU - Tomizawa, Yoko

AU - Kokaji, Toshiya

AU - Tanaka, Kaori Y.

AU - Uda, Shinsuke

AU - Suzuki, Y.

AU - Matsumoto, Masaki

AU - Nakayama, Keiichi

AU - Saitoh, Kaori

AU - Kato, Keiko

AU - Ueno, Ayano

AU - Ohishi, Maki

AU - Hirayama, Akiyoshi

AU - Soga, Tomoyoshi

AU - Kuroda, Shinya

PY - 2018

Y1 - 2018

N2 - The concentrations of insulin selectively regulate multiple cellular functions. To understand how insulin concentrations are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells using transcriptomic data, western blotting analysis of signaling proteins, and metabolomic data. By integrating sensitivity into the trans-omic network, we identified the selective trans-omic networks stimulated by high and low doses of insulin, denoted as induced and basal insulin signals, respectively. The induced insulin signal was selectively transmitted through the pathway involving Erk to an increase in the expression of immediate-early and upregulated genes, whereas the basal insulin signal was selectively transmitted through a pathway involving Akt and an increase of Foxo phosphorylation and a reduction of downregulated gene expression. We validated the selective trans-omic network in vivo by analysis of the insulin-clamped rat liver. This integrated analysis enabled molecular insight into how liver cells interpret physiological insulin signals to regulate cellular functions.

AB - The concentrations of insulin selectively regulate multiple cellular functions. To understand how insulin concentrations are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells using transcriptomic data, western blotting analysis of signaling proteins, and metabolomic data. By integrating sensitivity into the trans-omic network, we identified the selective trans-omic networks stimulated by high and low doses of insulin, denoted as induced and basal insulin signals, respectively. The induced insulin signal was selectively transmitted through the pathway involving Erk to an increase in the expression of immediate-early and upregulated genes, whereas the basal insulin signal was selectively transmitted through a pathway involving Akt and an increase of Foxo phosphorylation and a reduction of downregulated gene expression. We validated the selective trans-omic network in vivo by analysis of the insulin-clamped rat liver. This integrated analysis enabled molecular insight into how liver cells interpret physiological insulin signals to regulate cellular functions.

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