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Semicarbazide-sensitive amine oxidase substrates fail to induce insulin-like effects in fat cells from AOC3 knockout mice

  • Amine oxidases and disease
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Substrates of semicarbazide-sensitive amine oxidases (SSAO) stimulate glucose transport in adipocytes. To definitively demonstrate the involvement of SSAO in this insulin-like effect, glucose transport has been studied in fat cells from mice with a targeted deletion of AOC3, a gene encoding a SSAO called vascular adhesion protein-1. SSAO activity was present in white adipose tissues of wild type (WT) but was absent in AOC3KO mice. The SSAO-substrates benzylamine and methylamine were unable to stimulate hexose transport in adipocytes isolated from AOC3KO mice while they were active in WT adipocytes, especially in combination with vanadate. Impairment of amine-dependent glucose uptake was also observed with tyramine while there was no change in insulin responsiveness. These observations prove that the effects of exogenous or biogenic amines on glucose transport are not receptor-mediated but are oxidation-dependent. They also confirm that the major SSAO form expressed in mouse adipocytes is encoded by the AOC3 gene.

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Abbreviations

AOC2:

second gene encoding for amine oxidase, copper-containing

AOC3:

third gene for amine oxidase, copper-containing

INWAT:

intrabdominal white adipose tissues

KO:

knock-out

MAO:

monoamine oxidase

SCWAT:

subcutaneous white adipose tissues

SSAO/VAP-1:

semicarbazide-sensitive amine oxidase, vascular adhesion protein-1

WT:

wild-type

2-DG:

2-[1,2-3H]deoxyglucose

References

  • A Abella L Marti M Camps M Claret J Fernandez-Alvarez R Gomis A Guma N Viguerie C Carpéné M Palacin X Testar A Zorzano (2003) ArticleTitleSemicarbazide-sensitive amine oxidase/Vascular adhesion protein-1 activity exerts an antidiabetic action in Goto-Kakizaki rats Diabetes 52 1004–1013 10.2337/diabetes.52.4.1004 Occurrence Handle10.2337/diabetes.52.4.1004 Occurrence Handle1:CAS:528:DC%2BD3sXislOns7k%3D Occurrence Handle12663473

    Article  CAS  PubMed  Google Scholar 

  • C Carpéné S Bour D Prévot V Visentin P Valet (2005a) ArticleTitleMethylamine, ingested from food and additives, stimulates glucose transport and inhibits lipolysis in human adipose cells NAFAS 3 65–68

    Google Scholar 

  • C Carpéné S Bour V Visentin F Pellati S Benvenuti MC Iglesias-Osma MJ Garcia-Barrado P Valet (2005b) ArticleTitleAmine oxidase substrates for impaired glucose tolerance correction J Physiol Biochem 61 405–419 Occurrence Handle10.1007/BF03167058

    Article  Google Scholar 

  • C Carpéné D Daviaud J Boucher S Bour V Visentin S Grès C Duffaut E Fontana X Testar J-S Saulnier-Blache P Valet (2006) ArticleTitleShort- and long-term insulin-like effects of monoamine oxidase and semicarbazide-sensitive amine oxidase substrates in cultured adipocytes Metabolism 55 1397–1405 10.1016/j.metabol.2006.06.011 Occurrence Handle10.1016/j.metabol.2006.06.011 Occurrence Handle16979412 Occurrence Handle1:CAS:528:DC%2BD28Xps1ajuro%3D

    Article  PubMed  CAS  Google Scholar 

  • G Enrique-Tarancon L Marti N Morin JM Lizcano M Unzeta L Sevilla M Camps M Palacin X Testar C Carpéné A Zorzano (1998) ArticleTitleRole of semicarbazide-sensitive amine oxidase on glucose transport and GLUT 4 recruitment to the cell surface in adipose cells J Biol Chem 273 8025–8032 10.1074/jbc.273.14.8025 Occurrence Handle10.1074/jbc.273.14.8025 Occurrence Handle1:CAS:528:DyaK1cXitlOitLc%3D Occurrence Handle9525902

    Article  CAS  PubMed  Google Scholar 

  • G Enrique-Tarancon I Castan N Morin L Marti A Abella M Camps R Casamitjana M Palacin X Testar E Degerman C Carpéné A Zorzano (2000) ArticleTitleSubstrates of semicarbazide-sensitive amine oxidase co-operate with vanadate to stimulate tyrosine phosphorylation of insulin-receptor-substrates proteins, phosphoinositide-3-kinase activity and GLUT 4 translocation in adipose cells Biochem J 350 171–180 10.1042/0264-6021:3500171 Occurrence Handle10.1042/0264-6021:3500171 Occurrence Handle1:CAS:528:DC%2BD3cXmsVaqu78%3D Occurrence Handle10926841

    Article  CAS  PubMed  Google Scholar 

  • E Fontana J Boucher L Marti JM Lizcano X Testar A Zorzano C Carpéné (2001) ArticleTitleAmine oxidase substrates mimic several of the insulin effects on adipocyte differenciation in 3T3 F442A cells Biochem J 356 769–777 10.1042/0264-6021:3560769 Occurrence Handle10.1042/0264-6021:3560769 Occurrence Handle1:CAS:528:DC%2BD3MXkvVaqtLo%3D Occurrence Handle11389684

    Article  CAS  PubMed  Google Scholar 

  • S Garcia-Vicente A Abella N Viguerie A Ros-Baro M Camps X Testar M Palacin A Zorzano L Marti (2005) ArticleTitleThe release of soluble VAP-1/SSAO by 3T3-L1 adipocytes is stimulated by isoproterenol and low concentrations of TNFalpha J Physiol Biochem 61 395–401 Occurrence Handle10.1007/BF03167057 Occurrence Handle1:CAS:528:DC%2BD2MXhtFOht73J Occurrence Handle16180338

    Article  CAS  PubMed  Google Scholar 

  • A Heniquez G Meissonnier V Visentin D Prévot C Carpéné (2003) ArticleTitleHigh expression of semicarbazide-sensitive amine oxidase genes AOC2 and AOC3 but not the diamine oxidase gene AOC1 in human adipocytes Inflamm Res 52 IssueIDSuppl 1 S74–S75 10.1007/s000110300061 Occurrence Handle10.1007/s000110300061 Occurrence Handle1:CAS:528:DC%2BD3sXjsFSrtbY%3D Occurrence Handle12755418

    Article  CAS  PubMed  Google Scholar 

  • MC Iglesias-Osma MJ Garcia-Barrado V Visentin MF Pastor-Mansilla S Bour D Prévot P Valet J Moratinos C Carpéné (2004) ArticleTitleBenzylamine exhibits insulin-like effects on glucose disposal glucose transport, and fat cell lipolysis in rabbits and diabetic mice J Pharmacol Exp Ther 309 1020–1028 10.1124/jpet.103.063636 Occurrence Handle10.1124/jpet.103.063636 Occurrence Handle1:CAS:528:DC%2BD2cXksFCntrw%3D Occurrence Handle14978192

    Article  CAS  PubMed  Google Scholar 

  • MC Iglesias-Osma S Bour MJ Garcia-Barrado V Visentin MF Pastor X Testar L Marti G Enrique-Tarancon P Valet J Moratinos C Carpéné (2005) ArticleTitleMethylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism Pharmacol Res 52 475–484 10.1016/j.phrs.2005.07.008 Occurrence Handle10.1016/j.phrs.2005.07.008 Occurrence Handle1:CAS:528:DC%2BD2MXhtFyksbzF Occurrence Handle16135411

    Article  CAS  PubMed  Google Scholar 

  • S Jalkanen M Salmi (2001) ArticleTitleCell surface monoamine oxidases: enzymes in search of function EMBO J 20 3893–3901 10.1093/emboj/20.15.3893 Occurrence Handle10.1093/emboj/20.15.3893 Occurrence Handle1:CAS:528:DC%2BD3MXmtlChsb8%3D Occurrence Handle11483492

    Article  CAS  PubMed  Google Scholar 

  • N Mercier M Moldes K El Hadri B Fève (2001) ArticleTitleSemicarbazide-sensitive amine oxidase activation promotes adipose conversion of 3T3-L1 cells Biochem J 358 335–342 10.1042/0264-6021:3580335 Occurrence Handle10.1042/0264-6021:3580335 Occurrence Handle1:CAS:528:DC%2BD3MXmvFWntrg%3D Occurrence Handle11513731

    Article  CAS  PubMed  Google Scholar 

  • M Moldes B Fève J Pairault (1999) ArticleTitleMolecular cloning of a major mRNA species in murine 3T3 adipocyte lineage. Differentiation-dependent expression, regulation, and identification as semicarbazide-sensitive amine oxidase J Biol Chem 274 9515–9523 10.1074/jbc.274.14.9515 Occurrence Handle10.1074/jbc.274.14.9515 Occurrence Handle1:CAS:528:DyaK1MXisVWltbs%3D Occurrence Handle10092636

    Article  CAS  PubMed  Google Scholar 

  • N Morin JM Lizcano E Fontana L Marti F Smith P Rouet D Prévot A Zorzano M Unzeta C Carpéné (2001) ArticleTitleSemicarbazide-sensitive amine oxidase substrates stimulate glucose transport and inhibit lipolysis in human adipocytes J Pharmacol Exp Ther 297 563–572 Occurrence Handle1:CAS:528:DC%2BD3MXjt1WlsL0%3D Occurrence Handle11303044

    CAS  PubMed  Google Scholar 

  • N Morin V Visentin D Calise L Marti A Zorzano X Testar P Valet Y Fischer C Carpéné (2002) ArticleTitleTyramine stimulates glucose uptake in insulin-sensitive tissues in vitro and in vivo via its oxidation by amine oxidases J Pharmacol Exp Ther 303 1238–1247 10.1124/jpet.102.040592 Occurrence Handle10.1124/jpet.102.040592 Occurrence Handle1:CAS:528:DC%2BD38Xptlamu74%3D Occurrence Handle12438548

    Article  CAS  PubMed  Google Scholar 

  • Y Ochiai K Itoh E Sakurai Y Tanaka (2005) ArticleTitleMolecular cloning and characterization of rat semicarbazide-sensitive amine oxidase Biol Pharm Bull 28 413–418 10.1248/bpb.28.413 Occurrence Handle10.1248/bpb.28.413 Occurrence Handle1:CAS:528:DC%2BD2MXjsFehtb0%3D Occurrence Handle15744061

    Article  CAS  PubMed  Google Scholar 

  • M Salmi S Jalkanen (2005) ArticleTitleCell-surface enzymes in control of leukocyte trafficking Nat Rev Immunol 5 760–771 10.1038/nri1705 Occurrence Handle10.1038/nri1705 Occurrence Handle1:CAS:528:DC%2BD2MXhtVGrurvF Occurrence Handle16200079

    Article  CAS  PubMed  Google Scholar 

  • M Salmi S Tohka S Jalkanen (2000) ArticleTitleHuman vascular adhesion protein-1 (VAP-1) plays a critical role in lymphocyte-endothelial cell adhesion cascade under shear Circ Res 86 1245–1251 Occurrence Handle1:CAS:528:DC%2BD3cXks1KmtrY%3D Occurrence Handle10864915

    CAS  PubMed  Google Scholar 

  • I Sibon D Larrieu K El Hadri N Mercier B Feve P Lacolley C Labat D Daret J Bonnet JM Lamaziere (2004) ArticleTitleSemicarbazide-sensitive amine oxidase in annulo-aortic ectasia disease: relation to elastic lamellae-associated proteins J Histochem Cytochem 52 1459–1466 10.1369/jhc.4A6252.2004 Occurrence Handle10.1369/jhc.4A6252.2004 Occurrence Handle1:CAS:528:DC%2BD2cXhtVWgs7bM Occurrence Handle15505340

    Article  CAS  PubMed  Google Scholar 

  • DJ Smith M Salmi P Bono J Helmann T Leu S Jalkanen (1998) ArticleTitleCloning of vascular adhesion protein-1 reveals a novel multifunctional adhesion molecule J Exp Med 188 17–27 10.1084/jem.188.1.17 Occurrence Handle10.1084/jem.188.1.17 Occurrence Handle1:CAS:528:DyaK1cXksFOisLk%3D Occurrence Handle9653080

    Article  CAS  PubMed  Google Scholar 

  • CM Stolen GG Yegutkin R Kurkijarvi P Bono K Alitalo S Jalkanen (2004) ArticleTitleOrigins of serum semicarbazide-sensitive amine oxidase Circ Res 95 50–57 10.1161/01.RES.0000134630.68877.2F Occurrence Handle10.1161/01.RES.0000134630.68877.2F Occurrence Handle1:CAS:528:DC%2BD2cXlt1Cru7k%3D Occurrence Handle15178639

    Article  CAS  PubMed  Google Scholar 

  • CM Stolen F Marttila-Ichihara K Koskinen GG Yegutkin R Turja P Bono M Skurnik A Hanninen S Jalkanen M Salmi (2005) ArticleTitleAbsence of the endothelial oxidase AOC3 leads to abnormal leukocyte traffic in vivo Immunity 22 105–115 10.1016/j.immuni.2004.12.006 Occurrence Handle10.1016/j.immuni.2004.12.006 Occurrence Handle1:CAS:528:DC%2BD2MXht1Cgsb0%3D Occurrence Handle15664163

    Article  CAS  PubMed  Google Scholar 

  • C Subra E Fontana V Visentin X Testar C Carpéné (2003) ArticleTitleTyramine and benzylamine partially but selectively mimic insulin action on adipose differentiation in 3T3-L1 cells J Physiol Biochem 59 209–216 Occurrence Handle1:CAS:528:DC%2BD2cXjtFGksb8%3D Occurrence Handle15000452 Occurrence Handle10.1007/BF03179917

    Article  CAS  PubMed  Google Scholar 

  • PH Yu M Wang H Fan Y Deng D Gubisne-Haberle (2004) ArticleTitleInvolvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice Am J Physiol Endocrinol Metab 286 E634–E641 10.1152/ajpendo.00272.2003 Occurrence Handle10.1152/ajpendo.00272.2003 Occurrence Handle1:CAS:528:DC%2BD2cXjtlagur0%3D Occurrence Handle14656718

    Article  CAS  PubMed  Google Scholar 

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Bour, S., Prévot, D., Guigné, C. et al. Semicarbazide-sensitive amine oxidase substrates fail to induce insulin-like effects in fat cells from AOC3 knockout mice. J Neural Transm 114, 829–833 (2007). https://doi.org/10.1007/s00702-007-0671-2

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  • DOI: https://doi.org/10.1007/s00702-007-0671-2

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