Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism.

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO).

Substrates of semicarbazide-sensitive amine oxidase co-operate with vanadate to stimulate tyrosine phosphorylation of insulin-receptor-substrate proteins, phosphoinositide 3-kinase activity and GLUT4 translocation in adipose cells.

It has been shown that the combination of benzylamine or tyramine and low concentrations of vanadate markedly stimulates glucose transport in rat adipocytes by a mechanism that requires semicarbazide-sensitive amine oxidase (SSAO) activity and H(2)O(2) formation. Here we have further analysed the insulin-like effects of the combination of SSAO substrates and vanadate and we have studied the signal-transduction pathway activated in rat adipocytes. We found that several SSAO substrates (benzylamine, tyramine, methylamine, n-decylamine, histamine, tryptamine or beta-phenylethylamine), in combination with low concentrations of vanadate, stimulate glucose transport in isolated rat adipocytes.

Tyramine and vanadate synergistically stimulate glucose transport in rat adipocytes by amine oxidase-dependent generation of hydrogen peroxide.

Nonadrenergic imidazoline I2-binding sites colocalize with monoamine oxidase (MAO) in various tissues. As white adipocytes from various species have been reported to be very rich in I2-sites, the authors consider whether these cells show a substantial MAO activity and explore its functional role. Oxidation of [14C]tyramine by rat adipocyte membranes was dependent on both MAO and semicarbazide-sensitive amine oxidase (SSAO).

Role of semicarbazide-sensitive amine oxidase on glucose transport and GLUT4 recruitment to the cell surface in adipose cells.

The previous characterization of an abundant population of non-adrenergic imidazoline-I2 binding sites in adipocytes and the recent demonstration of the interplay between these binding sites and amine oxidases led us to analyze the amine oxidase activity in membranes from isolated rat adipocytes. Adipocyte membranes had substantial levels of semicarbazide-sensitive amine oxidase (SSAO). SSAO activity and immunoreactive SSAO protein were maximal in plasma membranes, and they were also detectable in intracellular membranes.

Chronic high-fat feeding and middle-aging reduce in an additive fashion Glut4 expression in skeletal muscle and adipose tissue.

The interaction of middle-aging and chronic high-fat feeding on glucose transport in skeletal muscle and adipose tissue was examined. To this end, we studied the effects of 6 month treatment with a high-fat diet in 12-month old rats. Chronic high-fat feeding led to a substantial reduction in GLUT4 glucose transporter expression both in adipose tissue and in skeletal muscle, which was additive to the reduction in GLUT4 protein content detected in aged rats.