The mechanisms by which the entero-insular axis influences -cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT, n=11) or impaired glucose tolerance (IGT, n=10), using C-peptide deconvolution to calculate insulin secretion rates, and mathematical modeling to quantitate -cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release (OGTT/IV ratio=1.59±0.18, p=0.004) amounted to 18±2 nmol^.m^-2 (or 32±4% of the oral response), and its time-course matched that of total insulin secretion. Both -cell glucose sensitivity (OGTT/IV ratio=1.52±0.26, p=0.02), rate sensitivity (or the response to glucose rate-of-change, OGTT/IV ratio=2.22±0.37, p=0.06) and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, -cell glucose sensitivity (75±14 vs 156±28 pmol^.min^-1.m^-2.mM^-1 of NGT, p=0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of: plasma GLP-1 and GIP responses, total insulin secretion, and enhancement of -cell glucose sensitivity (OGTT/IV ratio=1.73±0.24, p=ns vs NGT). However, the time-courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs incretin-mediated stimulation. We conclude that, under physiologic circumstances incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of -cell function, particularly -cell glucose sensitivity. In IGT, -cell function is inherently impaired, whereas the incretin effect is only partially affected.