Submitted on June 17, 2003
Accepted on November 19, 2003
Involvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice
Peter H. Yu1*, Michael Wang1, Hui Fan1, Yulin Deng1, and Diana Gubisne-Haberle1
1 Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
* To whom correspondence should be addressed. E-mail: YUP{at}USASK.CA.
Semicarbazide-sensitive amine oxidase (SSAO) is located on outer surfaces of
adipocytes, 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 on 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 substrates methylamine 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 to type II diabetes.
