Semicarbazide sensitive amine oxidase overexpression has dual consequences: insulin mimicry and diabetes-like complications.

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.

• 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)

Chemical References

• Blood Glucose
• Cell Adhesion Molecules
• Glycation End Products, Advanced
• Insulin
• Methylamines
• methylamine
• AOC3 protein, human
• Amine Oxidase (Copper-Containing)

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)