Islet amyloid polypeptide (amylin) increases the renal excretion of calcium in the conscious dog.

Islet amyloid polypeptide (IAPP) is a member of the calcitonin/CGRP family and has been isolated from the beta-cell of pancreatic islets. Recent evidence suggests that this peptide may be involved in calcium metabolism in that its administration resulted in lowering of serum calcium levels. To determine the mechanism of IAPP-induced hypocalcemia, the peptide was infused at 50 pmol/min/kg for 90 minutes in conscious male mongrel dogs. Infusion of the peptide resulted in a modest decline in the total serum calcium concentration (10.4 +/- 0.2 to 9.4 +/- 0.2 mg/dl; P < 0.05) and a concomitant increase in urinary calcium excretion (3.6 +/- 0.6 to 6.9 +/- 2.0 mg/dl; P < 0.01). Based on an extracellular volume of 7 liter in a 28 kg dog, the total decrement in calcium due to IAPP was 41.3 +/- 2.4 mg, whereas the total increase in urinary calcium was 3.2 +/- 0.7 mg. There were no detectable changes in calcitonin. We conclude that IAPP lowers serum calcium and increases the renal excretion of calcium independently of calcitonin. However, the calciuria can only account for a small component of the hypocalcemic effect and therefore, an additional calcium lowering effect of IAPP exits.