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ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Benzylamine Exhibits Insulin-Like Effects on Glucose Disposal, Glucose Transport, and Fat Cell Lipolysis in Rabbits and Diabetic Mice

Unité de recherches sur les obésités, Institut National de la Santé et de la Recherche Médicale U586, Institut Fédératif de Recherche 31, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France (V.V., S.B., D.P., P.V., C.C.); and Departamento de Fisiologia y Farmacologia, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain (M.C.I.-O., M.J.G.-B., M.F.P.-M., J.M.)

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 i.v. 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, whereas 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. 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.

Address correspondence to: Dr. Carpéné Christian; INSERM U586, IFR 31, Bat. L3, CHU Rangueil, 31403 Toulouse, France. E-mail: carpene{at}toulouse.inserm.fr

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