Amylin is a pancreatic islet beta-cell peptide hormone which modulates carbohydrate metabolism in skeletal muscle and liver, and could contribute to impaired insulin sensitivity in Type II diabetes. Here we report the first description of amylin secretion from isolated beta-cells. We measured amylin secretion from HIT T15 beta-cells exposed to glucose, arginine, glucagon, somatostatin, tolbutamide, glyburide, or metformin. With the exception of glucagon at concentrations above 1 microM, all compounds induced parallel, dose-dependent changes in secretion of amylin and insulin. We conclude that: 1) insulin and amylin are co-secreted from islet beta-cells; (2) nutrient secretagogues and peptide modulators exert direct effects on beta-cells to alter amylin and insulin secretion; (3) most modulators of islet beta-cell secretion alter amylin and insulin in parallel, but differential secretion can occur; and (4) HIT cell line is a useful model in which to study amylin metabolism.