title: A novel mechanism of glipizide sulfonylurea action: decreased metabolic clearance rate of insulin.
abstract: 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 microU/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 microU/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.
authors: Division of Endocrinology, Albert Einstein College of Medicine, New York, NY 10461, USA.
authors: N
authors: N
authors: Barzilai
authors: P H
authors: PH
authors: Groop
authors: L
authors: L
authors: Groop
authors: R A
authors: RA
authors: DeFronzo
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000097:blood*; D005260:Female; D005913:Glipizide / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose; D005913:Glipizide