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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on February 20, 2004; DOI: 10.1124/jpet.103.063636


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MARIA CARMEN IGLESIAS-OSMA
MARIA JOSE GARCIA-BARRADO
VIRGILE VISENTIN
MARIA FRANCISCA PASTOR-MANSILLA
SANDY BOUR
DANIELLE PREVOT
PHILIPPE VALET
JULIO MORATINOS
CHRISTIAN CARPENE
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Received for publication December 2, 2003.
Revised February 11, 2004.
Accepted for publication February 19, 2004.

BENZYLAMINE EXHIBITS INSULIN-LIKE EFFECTS ON GLUCOSE DISPOSAL, GLUCOSE TRANSPORT AND FAT CELL LIPOLYSIS IN RABBITS AND DIABETIC MICE

MARIA CARMEN IGLESIAS-OSMA 1, MARIA JOSE GARCIA-BARRADO 1, VIRGILE VISENTIN 2, MARIA FRANCISCA PASTOR-MANSILLA 1, SANDY BOUR 2, DANIELLE PREVOT 2, PHILIPPE VALET 2, JULIO MORATINOS 1, CHRISTIAN CARPENE 3*

1 Univ of Salamanca 2 Inserm U 586 3 INSERM U 586

* Address correspondence to: E-mail: carpene{at}toulouse.inserm.fr

Abstract

Benzylamine, a substrate of semicarbazide-sensitive amine oxidase (SSAO), stimulates glucose transport in rat adipocytes and improves glucose disposal in diabetic rats only in the presence of vanadate. These effects have been described to result from a synergism between the hydrogen peroxide formed during amine oxidation and vanadate, via the generation of pervanadate, a powerful insulin mimicker. However, it has also been reported that benzylamine alone can stimulate glucose uptake and inhibit lipolysis in human fat cells. In this work, we therefore investigated whether benzylamine on its own was able to induce both in vivo and in vitro insulin-like responses in animal models other than rat. In rabbits, the iv infusion of 7 µmol/kg benzylamine before a glucose tolerance test resulted in a net reduction of the hyperglycemic response without a change in insulin secretion. Benzylamine also improved glucose tolerance and reduced lipid mobilization in hyperglycemic/obese mice. In vitro, 0.1 mM benzylamine stimulated glucose transport and inhibited lipolysis in mouse and rabbit adipocytes. These effects were blocked by previous treatments with semicarbazide, a SSAO inhibitor. Levels of benzylamine oxidation were more elevated in mouse than in rabbit adipose tissues while the reverse was observed for skeletal muscles. Finally, benzylamine was unable to stimulate insulin secretion by isolated pancreatic islets from both species and SSAO activity was hardly detectable in pancreas. Taken together, our results bring evidence that benzylamine on its own can improve glucose tolerance in rabbit and mouse, likely by stimulating glucose uptake via amine oxidase activation in insulin-sensitive tissues.


Key words: adipose, amine oxidase, diabetes, glucose tolerance, insulin, lipolysis


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