Insulin-like effects of polyamines spermine binding to fat cells and fat cell membranes

Two naturally occurring polyamines, spermine and spermidine, mimic the action of insulin on lipid and glucose metabolism in adipocytes. To evaluate the role of cell membranes in the action of polyamines, studies of [¹⁴C] spermine binding using an oil separation method were conducted in isolated rat adipocytes and adipose cell membranes. Spermine binding and dissociation in fat cells and fat cell membranes were rapid and complete within 3–6 min. Following a 30-min incubation of [¹⁴C] spermine with fat cell membranes, over 90% of bound [¹⁴C] spermine was dissociable while under similar conditions only 25% of bound [¹⁴C] spermine was dissociable in cells. The non-dissociable fractions in cells likely represented intracellular accumulation. Binding and stimulation of glucose oxidation were demonstrated at similar concentrations. Bound spermine was displaced by spermine, spermidine and 1,8-diaminooctane with greater efficacy than putrescine (a polyamine devoid of insulin-like properties) or insulin. Similarly, polyamines did not complete with insulin for binding to isolated adipocytes. It appears, therefore, that polyamines initiate their insulin-like effects by interacting with the cell membrane at sites which are common to biologically active polyamines and which are distinct from the insulin receptor.