Although it is generally accepted that islet amyloid polypeptide is cosecreted with insulin, relatively few data on its kinetics are available. We therefore studied the dynamics of islet amyloid polypeptide release following oral and frequently sampled intravenous glucose tolerance tests in comparison to insulin and C-peptide using mathematical model techniques in 14 control subjects, 10 obese and 11 hypertensive patients. The fractional clearance rate of islet amyloid polypeptide (0.034 +/- 0.004 min-1 in control subjects, 0.058 +/- 0.008 in the obese and 0.050 +/- 0.008 in the hypertensive patients) was significantly different (p < 0.01) in each group compared with that of insulin (0.14 +/- 0.03 min-1) and similar to that of C-peptide (0.061 +/- 0.007 min-1), at least in the insulin-resistant subjects. Based on the insulin sensitivity index derived from the minimal model analysis of intravenous glucose tolerance test data, both the hypertensive (2.4 +/- 0.4 min-1/(microU/ml); p < 0.0005) and the obese (2.7 +/- 0.5; p < 0.001) patients demonstrated severe insulin resistance compared to control subjects (8.1 +/- 1.3). Marked insulin hypersecretion was found in the hypertensive (57.6 +/- 5.2 nmol.l-1 in 180 min; p < 0.001) and obese (60.8 +/- 10.1; p < 0.003) patients in comparison with control subjects (32.4 +/- 3.2). The release of islet amyloid polypeptide was significantly higher in the hypertensive (83.1 +/- 16.6 pmol/l in 180 min; p < 0.02) and obese (78.6 +/- 13.1; p < 0.005) patients than in control subjects (40.5 +/- 6.4). No correlation was found between islet amyloid polypeptide release and the insulin sensitivity index in any group.(ABSTRACT TRUNCATED AT 250 WORDS)