Abstract |
Semicarbazide-sensitive amine oxidases (SSAO) are copper-containing enzymes that oxidatively deaminate primary amines to produce hydrogen peroxide, ammonium, and specific aldehydes. Vascular adhesion protein-1 (VAP-1) is a cell surface and soluble molecule that possesses SSAO activity. VAP-1 protein, SSAO activity, and SSAO reaction products are elevated in the serum of patients with diabetes, congestive heart failure, and specific inflammatory liver diseases. By expressing human VAP-1/SSAO on mouse endothelial cells and subsequently in the serum, and by chronically treating the transgenic mice for 15 months with a high-fat diet and a physiological substrate for SSAO, methylamine, the in vivo roles of SSAO were assessed. The VAP-1 transgene increased the mouse body mass index and subcutaneous abdominal fat pad weights in a manner independent of food consumption. The transgene together with increased SSAO substrate availability enhanced glucose uptake in an SSAO-dependent manner. The increased SSAO activity also led to diabetes-like complications, including advanced glycation end product formation, elevated blood pressure, altered atherosclerosis progression, and nephropathy. These findings suggest that, although manipulation of VAP-1/SSAO has potential to serve as a therapeutic treatment in insulin-resistant conditions, care must be taken to fully understand its impact on obesity and vascular damage.
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Authors | Craig M Stolen, Rami Madanat, Luc Marti, Seppo Kari, Gennady G Yegutkin, Hannu Sariola, Antonio Zorzano, Sirpa Jalkanen |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 18
Issue 6
Pg. 702-4
(Apr 2004)
ISSN: 1530-6860 [Electronic] United States |
PMID | 14977883
(Publication Type: Journal Article)
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Chemical References |
- Blood Glucose
- Cell Adhesion Molecules
- Glycation End Products, Advanced
- Insulin
- Methylamines
- methylamine
- AOC3 protein, human
- Amine Oxidase (Copper-Containing)
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Topics |
- Amine Oxidase (Copper-Containing)
(chemistry, genetics, metabolism)
- Animals
- Arteriosclerosis
(etiology)
- Blood Glucose
(metabolism)
- Cell Adhesion Molecules
(chemistry, genetics, metabolism)
- Diabetic Angiopathies
(etiology)
- Diabetic Nephropathies
(etiology, pathology)
- Glycation End Products, Advanced
(biosynthesis)
- Humans
- Hypertension
(chemically induced, etiology)
- Hypertrophy
- Insulin
(chemistry)
- Kidney
(pathology)
- Methylamines
- Mice
- Mice, Transgenic
- Models, Biological
- Molecular Mimicry
- Obesity
(etiology)
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