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Published on: November 16, 2011
Semicarbazide-sensitive amine oxidase substrates fail to induce insulin-like effects in fat cells from AOC3 knockout
1Institut National de la Santé et de la Recherche Médicale, U586 INSERM, IFR 31, CHU Rangueil, Toulouse, France.
Abstract:
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.
Insights
Semicarbazide-sensitive amine oxidase (SSAO) substrates stimulate glucose uptake in fat cells. This study confirms SSAO, encoded by AOC3, is crucial for this insulin-like effect in mouse adipocytes.
Area of Science:
- Biochemistry
- Metabolic Research
- Cell Biology
Background:
- Substrates of semicarbazide-sensitive amine oxidases (SSAO) exhibit insulin-like effects by stimulating glucose transport in adipocytes.
- The precise mechanism and the specific SSAO involved in mediating this glucose uptake remain to be definitively elucidated.
Purpose of the Study:
- To investigate the role of vascular adhesion protein-1 (VAP-1), encoded by the AOC3 gene, in SSAO-mediated glucose transport in mouse adipocytes.
- To confirm that the observed effects of SSAO substrates on glucose uptake are oxidation-dependent and not receptor-mediated.
Main Methods:
- Utilized genetically modified mice with a targeted deletion of the AOC3 gene (AOC3KO).
- Assessed semicarbazide-sensitive amine oxidase (SSAO) activity in white adipose tissue from wild-type (WT) and AOC3KO mice.
- Measured hexose transport in adipocytes isolated from WT and AOC3KO mice in response to SSAO substrates (benzylamine, methylamine, tyramine) with and without vanadate.
Main Results:
- SSAO activity was detected in WT adipocytes but was absent in adipocytes from AOC3KO mice.
- Benzylamine and methylamine failed to stimulate hexose transport in AOC3KO adipocytes, whereas they were effective in WT cells, particularly with vanadate.
- Tyramine also showed impaired glucose uptake in AOC3KO adipocytes, while insulin responsiveness remained unchanged.
- These findings demonstrate that the major SSAO in mouse adipocytes is encoded by AOC3.
Conclusions:
- The AOC3 gene product, vascular adhesion protein-1, is the primary semicarbazide-sensitive amine oxidase (SSAO) responsible for stimulating glucose transport in mouse adipocytes.
- The insulin-like effect of SSAO substrates on glucose uptake is oxidation-dependent, not mediated by cell surface receptors.
- This study provides definitive evidence for the critical role of AOC3-encoded SSAO in regulating glucose metabolism in adipose tissue.
