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A novel mechanism of glipizide sulfonylurea action: decreased metabolic clearance rate of insulin

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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 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.

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Authors and Affiliations

  1. Division of Endocrinology, Albert Einstein College of Medicine, 701 Belfer Boulevard, 1300 Morris Park Avenue, 10461, New York, NY, USA

    N. Barzilai

  2. Fourth Department of Medicine, Helsinki University Hospital, Helsinki, Finland

    P. -H. Groop

  3. Department of Medicine, Malmo, Sweden

    L. Groop

  4. Department of Diabetes and Medicine, University of Texas at San Antonio, Texas, USA

    R. A. DeFronzo

Authors
  1. N. Barzilai
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  2. P. -H. Groop
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  3. L. Groop
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  4. R. A. DeFronzo
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Barzilai, N., Groop, P.H., Groop, L. et al. A novel mechanism of glipizide sulfonylurea action: decreased metabolic clearance rate of insulin. Acta Diabetol 32, 273–278 (1995). https://doi.org/10.1007/BF00576262

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  • DOI: https://doi.org/10.1007/BF00576262

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