Involvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice

Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E4 Submitted 17 June 2003 ; accepted in final form 19 November 2003 Semicarbazide-sensitive amine oxidase (SSAO) is located on outer surfaces of adipocytes and endothelial and vascular smooth muscle cells...

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Veröffentlicht in:American journal of physiology: endocrinology and metabolism 2004-04, Vol.286 (4), p.E634-E641
Hauptverfasser: Yu, Peter H, Wang, Michael, Fan, Hui, Deng, Yulin, Gubisne-Haberle, Diana
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Sprache:eng
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Zusammenfassung:Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E4 Submitted 17 June 2003 ; accepted in final form 19 November 2003 Semicarbazide-sensitive amine oxidase (SSAO) is located on outer surfaces of adipocytes and endothelial and vascular smooth muscle cells. This enzyme catalyzes deamination of methylamine and aminoacetone, leading to production of toxic formaldehyde and methylglyoxal, respectively, as well as hydrogen peroxide and ammonium. Several lines of evidence suggest that increased SSAO activity is related to chronic inflammation and vascular disorders related to diabetic complications. We found that a highly potent and selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine (FPFA), was capable of reducing numbers of atherosclerotic lesions as well as weight gain in obese KKAy mice fed an atherogenic diet. SSAO inhibitors cause a moderate and long-lasting hyperglycemia. Such an increase in serum glucose is a result of reduction of glucose uptake by adipocytes. SSAO-mediated deamination of endogenous methylamine substrates induces adipocyte glucose uptake and lipogenesis. Highly selective SSAO inhibitors can effectively block induced glucose uptake. The results suggest that increased SSAO-mediated deamination may be concomitantly related to obesity and vascular disorders associated with type 2 diabetes. semicarbazide-sensitive amine oxidase; methylamine; obesity; glucose uptake; diabetic complications Address for reprint requests and other correspondence: P. H. Yu, Neuropsychiatry Research Unit, Univ. of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E4 Canada.
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00272.2003