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			PubMed Journals: J Biol Chem

  Source:		PMID: 11912203


    		J Biol Chem. 2002 May 31;277(22):19521-9.
     		Epub 2002 Mar 23.

			Hydroxylation and glycosylation of the four
			conserved lysine residues in the collagenous
			domain of adiponectin. Potential role in
			the modulation of its insulin-sensitizing activity.

			Wang Y(1), Xu A, Knight C, Xu LY, Cooper
			GJ.

			Author Information
			(1) School of Biological Sciences, University
			of Auckland, Private Bag 92019, Auckland,
			1001 New Zealand.

			It has recently been shown that the fat-derived
			hormone adiponectin has the ability to decrease
			hyperglycemia and to reverse insulin resistance.
			However, bacterially produced full-length
			adiponectin is functionally inactive. Here,
			we show that endogenous adiponectin secreted
			by adipocytes is post-translationally modified
			into eight different isoforms, as shown
			by two-dimensional gel electrophoresis.
			Carbohydrate detection revealed that six
			of the adiponectin isoforms are glycosylated.
			The glycosylation sites were mapped to several
			lysines (residues 68, 71, 80, and 104) located
			in the collagenous domain of adiponectin,
			each having the surrounding motif of GXKGE(D).
			These four lysines were found to be hydroxylated
			and subsequently glycosylated. The glycosides
			attached to each of these four hydroxylated
			lysines are possibly glucosylgalactosyl
			groups. Functional analysis revealed that
			full-length adiponectin produced by mammalian
			cells is much more potent than bacterially
			generated adiponectin in enhancing the ability
			of subphysiological concentrations of insulin to
			inhibit gluconeogenesis in primary rat hepatocytes,
			whereas this insulin-sensitizing ability
			was significantly attenuated when the four
			glycosylated lysines were substituted with
			arginines. These results indicate that full-length
			adiponectin produced by mammalian cells
			is functionally active as an insulin sensitizer
			and that hydroxylation and glycosylation
			of the four lysines in the collagenous domain
			might contribute to this activity.

			DOI: 10.1074/jbc.M200601200 PMID: 11912203
			[Indexed for MEDLINE]

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