Evidence for Insulin Involvement in Arginine- and Glucose-Induced Hypercalciuria in the Rat

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Abstract
Urinary calcium excretion is increased after the consumption of protein and carbohydrate by both the human and the rat due to a decreased efficiency in the renal reabsorption of calcium. We have previously shown that the magnitude of the postprandial change in urine calcium in human subjects fed a high protein meal was correlated with the protein-induced changes in serum insulin levels. The present study investigates further the relationship between plasma insulin and urinary calcium excretion. Renal calcium clearance studies were performed in rats infused with the insulin secretagogues glucose or arginine, in the presence and absence of mannoheptulose, a drug which suppresses insulin secretion. The hypercalciuretic effect of arginine was also examined in streptozotocin (SZ) diabetic rats. Arginine and glucose infusion increased urinary calcium excretion by 575 and 225%, respectively, by a mechanism which could be inhibited by mannoheptulose. A linear relationship (r = 0.86) was observed between plasma insulin and urinary calcium excretion. Arginine infusion had no effect on urinary calcium excretion in the SZ diabetic rat, in marked contrast to its effect on normal animals. We conclude that insulin is an important mediator of arginine- and glucoseinduced hypercalciuria in the rat.