To examine whether sulfonylureas inhibit the metabolic clearance rate (MCR) of insulin, 19 healthy young subjects participated in two experiments. In the first protocol (n=10), a 3-h oral glucose load was performed with and without 2 mg of glipizide given 30 min before glucose ingestion. The total insulin response was 60% greater with than without glipizide (5.9±0.6 vs 3.7±0.5 μU/ml;P<0.001). However, the total C-peptide responses were virtually identical (4.7±0.5 vs 4.8±0.4 nmol/l) in both studies. In the second protocol (n=9), the MCR of insulin was measured during 4-h euglycemic insulin clamps performed with and without glipizide. In the study with glipizide, the subjects ingested 5 mg of glipizide at 120 min. The steady-state plasma insulin concentration during the 4th h, i.e., 1-2 h after glipizide ingestion, was significantly higher than during the 2nd h, i.e., before glipizide ingestion (99±22 vs 78±17 μU/ml;P<0.01). In addition, glucose uptake during the 4th h was greater (8.0±1.6 vs 6.4±1.5 mg/kg·min) and the MCR of insulin was reduced (503±126 vs 621±176 ml/m2·min;P<0.01). We conclude that glipizide augments plasma insulin levels both by enhancing its secretion and by decreasing the MCR of insulin.
- Insulin metabolic clearance rate (MCR)
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism