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			PubMed Journals: Zoolog Sci

  Source:		PMID: 15738637


    		Zoolog Sci. 2005 Feb;22(2):169-75.
     
			Receptor-type protein tyrosine phosphatase
			epsilon (PTPepsilonM) is a negative regulator
			of insulin signaling in primary hepatocytes
			and liver.

			Nakagawa Y(1), Aoki N, Aoyama K, Shimizu
			H, Shimano H, Yamada N, Miyazaki H.

			Author Information
			(1) Gene Research Center, University of
			Tsukuba, Japan.

			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
			PTPepsilon (PTP epsilonM) dephosphorylated
			IR in rat primary hepatocytes and tyrosines
			972, 1158, 1162 and 1163 were primary targets
			of PTP epsilonM. Wild type as well as
			substrate-trapping DA forms of PTPepsilonM
			suppressed phosphorylation of IR downstream
			enzymes such as Akt, extracellular regulated
			kinase (ERK) and glycogen synthase kinase
			3 (GSK3). It was also demonstrated that
			PTPepsilonM suppressed insulin-induced glycogen
			synthesis and inhibited insulin-induced
			suppression of phosphoenol pyruvate carboxykinase
			(PEPCK) expression in primary hepatocytes.
			Furthermore, adenovirally introduced PTPepsilonM
			also exhibited inhibitory activity against
			suppression of PEPCK expression in mouse
			liver. These results suggest that PTPepsilonM
			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.

			DOI: 10.2108/zsj.22.169 PMID: 15738637
			[Indexed for MEDLINE]

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