This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (SG), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled i.v. glucose tolerance test was performed in 20 elderly (E, 10/10 male/female, all 63 yr old) and in 20 young subjects (Y, 10/10 male/female, all 27 yr old), who were similar in body mass index and 2-h blood glucose during oral glucose tolerance test. E exhibited impaired glucose elimination (i.v. tolerance index, 1.31 +/- 0.10 vs. 1.70 +/- 0.12% min-1; P = 0.019). First-phase insulin secretion and SI did not differ between the groups, whereas E had lower glucose sensitivity of second-phase insulin secretion (0.40 +/- 0.07 vs. 0.70 +/- 0.08 (pmol/L)min-2/(mmol/L), P = 0.026), lower SG, 0.017 +/- 0.002 vs. 0.025 +/- 0.002 min-1, P = 0.004), and higher HE (81.3 +/- 2.4 vs. 73.2 +/- 2.1%, P = 0.013). Across both groups, SG correlated positively with glucose tolerance index (r = 0.58, P < 0.001) and negatively with HE (r = -0.54, P < 0.001). Plasma leptin and glucagon did not change by age, whereas plasma pancreatic polypeptide (PP) was higher in E (122 +/- 18 vs. 66 +/- 6 pg/mL, P = 0.004). PP did not, however, correlate to any other parameter. We conclude that E subjects with normal oral glucose tolerance have reduced SG, impaired second-phase insulin secretion, and increased HE, whereas SI and first-phase insulin secretion seem normal. SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.