Improved glucose disposal after repeated intravenous (IV) glucose loads, known as the Staub effect, is absent in both type I and type II diabetes. Acute decrements of insulin secretion (AID) are observed following the early phase of insulin release on IV glucose stimulation in non-insulin-dependent diabetes mellitus (NIDDM). The AID cannot be corrected by acute infusions of glyburide or glipizide, or phentolamine, or by glycemic control after 2 weeks of intensive insulin treatments. Fifteen male subjects had 3 hourly successive IV glucose tolerance tests before and after 6 months of glipizide, at a final maintenance dose of 30 +/- 3 mg/d. Before treatment, AID, defined as the difference of the lowest of post IV glucose 7- or 10-minute samples from the preceding baseline insulin levels, was detected in the three loads: -6.4 +/- 1.9 microU/mL in the first, and then more consistently in the second and third loads, -11 +/- 2 microU/mL, and -17 +/- 9 microU/mL, respectively. There was a stepwise increase in insulin sums after each load. After glipizide therapy, the AIDS following all three IV glucose loads were no longer demonstrable; both insulin values, as well as insulin sums, were significantly elevated after all three glucose loads. While in the untreated state, the Staub effect was absent: serum glucose disappearances (K), corrected for glycosuria, were K1 = 0.52 +/- 0.02, K2 = 0.50 +/- 0.04, and K3 = 0.52 +/- 0.03.(ABSTRACT TRUNCATED AT 250 WORDS)