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

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 i.v. infusion of 7 mol/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.

Exercise training decreases in vitro stimulated lipolysis in a visceral (mesenteric) but not in the retroperitoneal fat depot of high-fat-fed rats

“…Basal and stimulated lipolysis was determined in isolated adipocytes (50 ml) incubated with a 10 ul solution of KRBA buffer and ascorbic acid (basal) and with isoproterenol adjusted to give concentrations of 10 27 , 10 25 and 10 24 M. Isoproterenol was used because it is a pure b-agonist and as such it elicits the greatest lipolytic response (8) . Isoproterenol produced a dosedependent increase in lipolysis, with the maximal responses (plateau) reached at 10 24 and 10 25 M. In agreement with other groups, adenosine deaminase was not added to the incubation medium to block the anti-lipolytic action of adenosine (21,22) . The incubation was performed at 378C under a 95 % O 2 -5 % CO 2 atmosphere with gentle shaking (eighty strokes per min) for 2 h. The reaction was stopped by adding 50 ml HCl (1 M) and then 50 ml NaOH (1 M) to neutralise the medium.…”

Differential sensitivity to adrenergic stimulation underlies the sexual dimorphism in the development of diabetes caused by Irs-2 deficiency

“…The details of this experimental procedure have been described previously [37]. Briefly, intra-abdominal white adipose tissue (WAT) of perirenal and epididymal origin was removed from fed animals.…”

Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

“…However, in our model MAO inhibition did not modify glucose or BU 224 mediated insulin release. At this point it is interesting to note that the total capacity of the pancreas to oxidise MAO substrates was limited compared with the overall mass and amine oxidase activities of muscular and adipose tissue [43]. Therefore these results reassess the true nature of BU 224 as an I 2 ligand, though the response under study seems to be independent of MAO binding sites.…”