Hypocalcemia reduces insulin turnover but not insulin-mediated glucose metabolism in piglets.

Abstract

Disturbances of glucose metabolism similar to type II diabetes are often accompanied by low extra cellular calcium concentrations, as shown in periparturient ruminants. Hypocalcemia reduces insulin secretion and possibly endogenous glucose production, but whether hypocalcemia also affects peripheral actions of insulin is not clear. The problem was investigated with piglets in this study. Insulin-mediated turnover of glucose and the clearance of insulin were measured in 7 control piglets (+D) and in 10 piglets with inherited calcitriol deficiency (-D). The measurements involved continuous intravenous infusions of insulin (1, 2, 5, 7.5 and 10 mU x kg(-1) x min(-1)) and glucose to maintain a glucose concentration of 7 mmol x l(-1) (combined insulin and glucose clamps). Both groups of piglets were studied under normo- and hypocalcemic conditions. During hypocalcemia and with equal insulin infusion rates, -D and +D piglets attained significantly higher (28%-133%) steady state insulin concentrations in plasma than during normocalcemia. This showed that the clearance rates of insulin during hypocalcemia were 48% lower in +D and 20% lower in -D piglets than during normocalcemia. With equivalent insulin infusion rates +D piglets developed significantly higher (15%-48%) steady state insulin concentrations in plasma than -D piglets, indicating that the clearance rate of insulin was higher in the calcitriol-deficient state. The relationship between insulin concentration in plasma and glucose turnover (measured with [3-(3)H]glucose) was not influenced by the calcemic and vitamin D status of the piglets. This indicated that the peripheral action of insulin on glucose metabolism was not influenced by the extracellular calcium concentration and vitamin D status.