The relationship between early insulin release and glucose tolerance in healthy subjects.

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Therefore insulin and C-peptide responses to oral glucose were measured in healthy subjects with and without a single dose of oral and intravenous glipizide. The intravenous glipizide administration caused a marked early insulin response, whereas oral glipizide administration resulted in greater total and peak insulin concentration. Oral glipizide did not reduce plasma glucose until 45 min of the glucose load. In contrast, enhancement of the early insulin response with intravenous glipizide almost completely prevented postprandial glucose rise. In conclusion, early insulin release is a major factor determining oral glucose tolerance in healthy subjects.