Effect of Copper on Insulin Release by the Intact Rat Pancreas and the Perfused Rat Pancreas

Abstract

In previous studies, we have shown that rats fed a copper-poor diet have an impaired glucose tolerance and insulin response to an oral glucose load. Furthermore, CuCl2 X 2H2O added to the incubation medium stimulated glucose incorporation into the diaphragm glycogen and epididimal fat of rats. The purpose of the present study was to examine the effect of copper on insulin release in vivo and in the perfused pancreas. Copper chloride stimulated the insulin release by the perfused pancreas of rats fed laboratory chow (copper content, 6.7 ppm). Stimulation with 0.5 mg/dl CuCl2 X 2H2O for 20 min resulted in release of 14.7 +/- 3.1 compared with 18.9 +/- 4.3 mu insulin following stimulation with 16.7 mM glucose. The CuCl2 X 2H2O effect depended on the presence of calcium in the medium--as with other insulinotropic agents--but not on the presence of magnesium. Animals fed a copper-poor (1.2 ppm) sucrose diet have a selective impairment to i.v. glucose-induced insulin stimulation, but not to i.v. arginine or aminophylline stimulation when compared with controls fed a sucrose copper-supplemented diet or a laboratory chow diet. This selective beta cell defect is not necessarily genetically inherited and may be acquired. The role of copper on insulin release is discussed.