Studies of the Insulin-like Actions of Polyamines on Lipid and Glucose Metabolism in Adipose Tissue Cells

Two naturally occurring polyamines, spermidine and spermine, mimicked the actions of insulin on lipid and glucose metabolism in isolated rat adipocytes. In the concentration range of 0.001 to 0.1 mm, spermidine and spermine suppressed lipolysis and stimulated conversion of glucose to carbon dioxide. Structure-function studies revealed that the insulin-mimicking properties of polyamines are dependent upon a spatial separation of amino groups. Putrescine (1,4-butanediamine) and 1,3-propanediamine possessed no insulin-like properties. Diamines separated by 5 or 6 carbon atoms were slightly effective whereas those separated by 7 or more carbon atoms were as potent as spermidine. Maximal insulin-like actions of polyamines were shown only in the presence of bovine serum albumin (Fraction V) which was shown to contain amine oxidase activity. Exposure of bovine albumin to EDTA or dialysis markedly decreased the effects of spermidine without influencing insulin effects or amine oxidase activity. The actions of spermidine were also absent in the presence of ovine serum albumin although amine oxidase activity was present. Furthermore, addition of purified amine oxidase to the fat cell incubation preferentially inhibited the actions of spermidine suggesting that the insulin-like properties of these compounds are not mediated through aldehyde products formed by amine oxidase present in bovine serum. Digestion of adipocytes with trypsin which leads to modifications of the insulin-receptor system on the membrane, did not affect the cellular response to spermidine. In contrast, treatment of isolated adipose tissue cells with neuraminidase from Clostridium perfringens abolished the action of both insulin and spermidine on glucose metabolism and lipolysis, but did not alter basal glucose utilization or theophylline-induced lipolysis. Spermidine and spermine (1.0 mm) did not compete with insulin for binding to isolated fat cells. The results of the cellular enzymatic modifications and binding studies indicate that polyamines mimic the action of insulin subsequent to the insulin receptor site.