Is copper effect on glucose incorporation mediated by the insulin receptor in rat adipose tissue?

The insulin receptor is not the site for the stimulatory effect of copper on glucose incorporation into total lipids by adipose tissue; prewashing of adipose tissue of rats fed a stock diet in an insulin-free medium increases the glucose incorporation into total lipids in the presence of 0.1 unit insulin from 220 above control to 430% in the nondiabetic and from 154 to 230% in the streptozotocin-diabetic rat. In contrast, glucose incorporation in the presence of CuCl2 X 2H2O is unaffected by prewashing, being the same in the prewashed as in the unwashed adipose tissue. On the other hand, mild trypsin digestion of adipocytes decreases the glucose incorporation in the presence of 28.5 mU insulin, from 201 to 126% - whereas the effect of copper on glucose incorporation is the same in the trypsin-treated or untreated adipocyte. In order to obtain maximal copper effect the adipocyte has to be preconditioned by insulin; preincubation of diabetic adipose tissue first for one hour with 0.1 unit insulin, and another hour with 100 micrograms CuCl2 X 2H2O added to the medium, results in greater glucose incorporation (230% above control) than when incubated alone with either CuCl2 X 2H2O (125%) or insulin (154%) for two hours. In addition to its previously noted effect on the in vivo insulin release, copper increased the number of the insulin receptor sites in adipocytes.