| RRC ID |
41887
|
| 著者 |
Kishida K, Nagaretani H, Kondo H, Kobayashi H, Tanaka S, Maeda N, Nagasawa A, Hibuse T, Ohashi K, Kumada M, Nishizawa H, Okamoto Y, Ouchi N, Maeda K, Kihara S, Funahashi T, Matsuzawa Y.
|
| タイトル |
Disturbed secretion of mutant adiponectin associated with the metabolic syndrome.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and complement C1q-like globular domains, and circulates in human plasma in a multimeric form. The protein exhibits anti-diabetic and anti-atherogenic activities. However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia. We have recently reported a missense mutation in the adiponectin gene, in which isoleucine at position 164 in the globular domain is substituted with threonine (I164T). Subjects with this mutation showed markedly low level of plasma adiponectin and clinical features of the metabolic syndrome. Here, we examined the molecular characteristics of the mutant protein associated with a genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant protein showed an oligomerization state similar to the wild-type as determined by gel filtration chromatography and, (2) the mutant protein exhibited normal insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion of the mutant protein from adipose tissues. Our results suggest that I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome.
|
| 巻・号 |
306(1)
|
| ページ |
286-92
|
| 公開日 |
2003-6-20
|
| DOI |
10.1016/s0006-291x(03)00940-9
|
| PII |
S0006291X03009409
|
| PMID |
12788102
|
| MeSH |
Adiponectin
Adipose Tissue / metabolism
Amino Acid Sequence
Cell Line
Conserved Sequence
Humans
Immunochemistry
Intercellular Signaling Peptides and Proteins*
Metabolic Syndrome / blood
Metabolic Syndrome / genetics*
Metabolic Syndrome / physiopathology*
Mutation, Missense*
Protein Structure, Quaternary
Proteins / chemistry
Proteins / genetics*
Proteins / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sequence Homology, Amino Acid
Species Specificity
Transfection
|
| IF |
2.985
|
| 引用数 |
55
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
