Combined treatment with benzylamine and low dosages of vanadate enhances glucose tolerance and reduces hyperglycemia in streptozotocin-induced diabetic rats.
Semicarbazide-sensitive amine oxidase (SSAO) is highly expressed in adipose cells, and substrates of SSAO, such as benzylamine, in combination with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 recruitment in 3T3-L1 and rat adipocytes. Here we examined whether acute and chronic administration of benzylamine and vanadate in vivo enhances glucose tolerance and reduces hyperglycemia in diabetic rats. Acute intravenous administration of these drugs enhanced glucose tolerance in nondiabetic rats and in streptozotocin (STZ)-induced diabetic rats. This occurred in the absence of changes in plasma insulin concentrations. However, the administration of benzylamine or vanadate alone did not improve glucose tolerance. The improvement caused by benzylamine plus vanadate was abolished when rats were pretreated with the SSAO-inhibitor semicarbazide. Chronic administration of benzylamine and vanadate exerted potent antidiabetic effects in STZ-induced diabetic rats. Although daily administration of vanadate alone (50 and 25 micromol x kg(-1) x day(-1) i.p.) for 2 weeks had little or no effect on glycemia, vanadate plus benzylamine reduced hyperglycemia in diabetic rats, enhanced basal and insulin-stimulated glucose transport, and upregulated GLUT4 expression in isolated adipocytes. In all, our results substantiated that acute and chronic administration of benzylamine with low dosages of vanadate have potent antidiabetic effects in rats.
Marti
L
L
Departament de Bioquìmica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Abella
A
A
Carpéné
C
C
Palacín
M
M
Testar
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X
Zorzano
A
A
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005947:Glucose / Q000502:physiology; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000209:etiology*; D051275:Glucose Transporter Type 4; D006943:Hyperglycemia / Q000188:drug therapy*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides / Q000494:pharmacology; D014638:Vanadates / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000627:therapeutic use
D001596:Benzylamines; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012663:Semicarbazides; C495694:Slc2a4 protein, rat; C010059:carbamylhydrazine; D014638:Vanadates; C030796:benzylamine; D005947:Glucose