Islet amyloid polypeptide (IAPP) or amylin is a 37 amino-acid peptide involved in carbohydrate metabolism. It is a hormone secreted from the pancreatic cells which is reported to be co-secreted with insulin. Its function and secretion is not well known. A paracrine inhibition of insulin secretion could be the main function of this hormone. Different hypotheses are considered regarding IAPP co-localization with insulin in the secretory granules and its subsequent secretion. In the attempt to clarify these controversial findings we evaluated the plasma concentrations of IAPP and insulin during different intravenous glucose administrations in healthy patients. Twenty normoglycemic patients (10 females, 10 males, age +/- SD 37 +/- 9 years) underwent two different endovenous glucose administrations: a) "long duration" infusion, in which 500 ml of 33% glucose solution was administered in 60 minutes, b) a standard intra-venous glucose tolerance test (IVGTT) characterized by an infusion of 0.33 g/Kg of glucose in 4 minutes. Blood samples were collected at fixed times (from 0 to 180 minutes) to assay IAPP, insulin and glucose concentration. The IAPP secretion seemed to be related more to the glycemic variation than to the insulin secretion. A proportional behavior of IAPP and insulin was observed only in the first 90 minutes of the long duration infusion. The highest increases of IAPP concentrations were found when there was a rapid glucose decrease in the blood. These findings suggest a significant role of IAPP in regulating the rapid decreases of glycemia.