Receptor-Type Protein Tyrosine Phosphatase ε (PTPεM) is a Negative Regulator of Insulin Signaling in Primary Hepatocytes and Liver
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概要
- 論文の詳細を見る
Impaired insulin receptor (IR) signaling leads to insulin resistance and type 2 diabetes mellitus. Several inhibitors of the IR tyrosine kinase activity have recently been described and associated with human insulin resistance. Among these negative regulators, protein tyrosine phosphatases (PTPs) are likely to play a pivotal role in IR signaling. Transgenic studies revealed that PTP1B and TCPTP are primary candidates but IR of these animals can be finally dephosphorylated, suggesting that other PTPs are also involved in the dephosphorylation of IR. In this study, we showed that receptor-type PTPε (PTP εM) dephosphorylated IR in rat primary hepatocytes and tyrosines 972, 1158, 1162 and 1163 were primary targets of PTP εM. Wild type as well as substrate-trapping DA forms of PTPεM suppressed phosphorylation of IR downstream enzymes such as Akt, extracellular regulated kinase (ERK) and glycogen synthase kinase 3 (GSK3). It was also demonstrated that PTPεM suppressed insulin-induced glycogen synthesis and inhibited insulin-induced suppression of phosphoenol pyruvate carboxykinase (PEPCK) expression in primary hepatocytes. Furthermore, adenovirally introduced PTPεM also exhibited inhibitory activity against suppression of PEPCK expression in mouse liver. These results suggest that PTPεM is a negative regulator of IR signaling and involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver.
- 社団法人日本動物学会の論文
- 2005-02-25
著者
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YAMADA Nobuhiro
Department of Internal Medicine, University of Tsukuba
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Shimano Hitoshi
筑波大学 人間総合科学研究科代謝内分泌学
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Shimano Hitoshi
Advanced Biomedical Applications Graduate School Of Comprehensive Human Sciences Univ. Of Tsukuba 1-
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Nakagawa Yoshimi
Gene Research Center, University of Tsukuba
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Aoki Naohito
Department of Life Sciences, Faculty of Bioresources, Mie University
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Aoyama Koji
Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya Uni
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Shimizu Hidehisa
Gene Research Center, University of Tsukuba
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Shimano Hitoshi
Tsukuba Advanced Research Alliance (TARA) Center, University of Tsukuba
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Miyazaki Hitoshi
Gene Research Center, University of Tsukuba
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Yamada Nobuhiro
The Research Committee For Primary Hyperlipidemia Research On Measures For Intractable Diseases By T
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Yamada Nobuhiro
Department Of Internal Medicine University Of Tsukuba Institute Of Clinical Medicine
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Yamada Nobuhiro
筑波大学 人間総合科学研究科代謝内分泌学
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Aoki Naohito
Department Of Life Sciences Faculty Of Bioresources Mie University
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Aoki Naohito
Department Of Applied Biological Sciences School Of Agricultural Sciences Nagoya University
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Yamada Nobuhiro
Department Of Internal Medicine (endocrinology And Metabolism) Graduate School Of Comprehensive Huma
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Yamada Nobuhiro
Department Of Internal Medicine Institute Of Clinical Medicine University Of Tsukuba
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Shimano Hitoshi
Tsukuba Advanced Research Alliance (tara) Center University Of Tsukuba:department Of Internal Medici
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Shimano Hitoshi
Department Of Metabolic Diseases Faculty Of Medicine University Of Tokyo
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Miyazaki Hitoshi
Gene Experiment Center Institute Of Applied Biochemistry
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Shimizu Hidehisa
Gene Research Center University Of Tsukuba
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Nakagawa Yoshimi
Gene Research Center University Of Tsukuba:tsukuba Advanced Research Alliance (tara) Center Universi
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Yamada Nobuhiro
Department Of Chemistry And Chemical Engineering Yamagata University
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Miyazaki Hitoshi
Univ. Tsukuba Ibaraki Jpn
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Aoyama Koji
Department Of Applied Molecular Biosciences Graduate School Of Bioagricultural Sciences Nagoya Unive
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Yamada Nobuhiro
Department Of Metabolic Diseases Faculty Of Medicine University Of Tokyo
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Yamada Nobuhiro
Department Of Internal Medicine (endocrinology And Metabolism) Graduate School Of Comprehensive Huma
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Yamada Nobuhiro
Department Of Internal Medicine (endocrinology And Metabolism) Graduate School Of Comprehensive Huma
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Yamada Nobuhiro
Department Of Internal Medicine (endocrinology And Metabolism) Graduate School Of Comprehensive Huma
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