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
(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]