Semicarbazide-sensitive amine oxidase activity exerts insulin-like effects on glucose metabolism and insulin-signaling pathways in adipose cells.
Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. Moreover, the acute administration of benzylamine and vanadate in vivo enhances glucose tolerance in non-diabetic and streptozotocin-induced diabetic rats and reduces hyperglycemia after chronic treatment in streptozotocin-diabetic rats. Based on these observations, we propose that SSAO activity and vanadate potently mimic insulin effects in adipose cells and exert an anti-diabetic action in an animal model of type 1 diabetes mellitus.
Zorzano
Antonio
A
Facultat de Biologia, Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Avda. Diagonal 645, 08028 Barcelona, Spain. azorzano@porthos.bio.ub.es
Abella
Anna
A
Marti
Luc
L
Carpéné
Christian
C
Palacín
Manuel
M
Testar
Xavier
X
D017667:Adipocytes / Q000378:metabolism*; D006631:Amine Oxidase (Copper-Containing) / Q000502:physiology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D012663:Semicarbazides / Q000494:pharmacology*; D015398:Signal Transduction; D014638:Vanadates / Q000494:pharmacology
D001596:Benzylamines; C526292:IRS1 protein, human; C491585:IRS3P protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C491584:Irs3 protein, rat; D010750:Phosphoproteins; D012663:Semicarbazides; D014638:Vanadates; C030796:benzylamine; D006631:Amine Oxidase (Copper-Containing); D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose