Involvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice.
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.
Yu
Peter H
PH
Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E4.
Wang
Michael
M
Fan
Hui
H
Deng
Yulin
Y
Gubisne-Haberle
Diana
D
D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001693:Biological Transport, Active; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D003641:Deamination; D003847:Deoxyglucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009765:Obesity / Q000201:enzymology / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D001596:Benzylamines; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D003847:Deoxyglucose; C030796:benzylamine; D006631:Amine Oxidase (Copper-Containing); D005947:Glucose