The Mechanism of Insulin-Induced Hypercalcemia in the Chick*

Previous work by our laboratory has shown that insulin provokes a dose-related hypercalcemia in chicks. To study some of the possible mechanisms responsible for this effect, the role of intestinal absorption of Ca and the participation of the skeleton in the insulin-induced hypercalcemia were investigated. Two experiments were conducted for determining the role of intestinal absorption of Ca. 1) Six-day-old chicks were maintained on a Ca-deficient diet for 7 days. At 13 days of age, the administration of insulin (0.2 U, iv) provoked a significant elevation of plasma Ca (P < 0.01) similar to the increase observed in birds maintained on regular laboratory diet. 2) The effect of the same dose of insulin on intestinal 47Ca absorption was studied using a ligated intestinal loop preparation in vivo. Although significant hypercalcemia occurred (P < 0.001), the absorption of 47Ca was not enhanced. No change was observed in plasma radioactivity, but a significant decrease (P < 0.01) in tibia 47Ca was observed 25 min after the administration of insulin. The integrity of the intestinal loop preparation was assessed by determining the effect of 1,25-dihydroxyvitamin D3 on 47Ca absorption. A 4-fold increase in intestinal 47Ca was observed after the administration of 0.2 μg 1,25-dihydroxyvitamin D3 to vitamin D-deficient chicks. The possibility of the participation of the skeleton in insulininduced hypercalcemia was studied in chicks given sc injections of 10 μCi 45Ca/day for 3 days. Intravenous administration of insulin resulted in a significant increase (P < 0.05) in 45Ca in plasma and a decrease (P < 0.05) in 45Ca in bone. The data suggest that the hypercalcemic effect of insulin in chicks is mediated by an acute mobilization of Ca from the skeleton, probably by acting on the readily available exchangeable bone Ca, in avian species.