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Original Articles

Glucagon-Like Peptide 1 Improves the Ability of the β-Cell to Sense and Respond to Glucose in Subjects With Impaired Glucose Tolerance

  1. Maria M Byrne,
  2. Katja Gliem,
  3. Uwe Wank,
  4. Rudolf Arnold,
  5. Martin Katschinski,
  6. Kenneth S Polonsky and
  7. Burkhard Goke
  1. Clinical Research Unit of Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps University Marburg, Germany
  2. Department of Medicine, The University of Chicago and Pritzker School of Medicine Chicago, Illinois
  1. Address correspondence and reprint requests to Dr. Maria M. Byrne, Clinical Research Unit for Gastrointestinal Endocrinology, Department of Internal Medicine, Philipps University, 35033 Marburg, Germany. E-mail: byrnem{at}mailer.uni-marburg.de
Diabetes 1998 Aug; 47(8): 1259-1265. https://doi.org/10.2337/diab.47.8.1259
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Abstract

Impaired glucose tolerance (IGT) and NIDDM are both associated with an impaired ability of the β-Cell to sense and respond to small changes in plasma glucose concentrations. The aim of this study was to establish if glucagon-like peptide 1 (GLP-1), a natural enteric peptide and potent insulin secretagogue, improves this defect. Two weight-matched groups, one with eight subjects having IGT (2-h glucose, 10.1 ± 0.3 mmol/l) and another with seven subjects with diet-treated NIDDM (2-h glucose, 14.5 ± 0.9 mmol/l), were studied on two occasions during a 12-h oscillatory glucose infusion, a sensitive test of the ability of the β-Cell to sense and respond to glucose. Glucose was infused with a mean rate of 4 mg · kg−1 · min−1, amplitude 33% above and below the mean rate, and periodicity of 144 min, with infusion of saline or GLP-1 at 0.4 pmol · kg−1 · min−1 for 12 h. Mean glucose levels were significantly lower in both groups during the GLP-1 infusion compared with during saline infusion: 9.2 ± 0.4 vs. 6.4 ±0.1 mmol/l in the IGT subjects (P < 0.0004) and 14.6 ± 1.0 vs. 9.3 ± 0.7 mmol/L in NIDDM subjects (P < 0.0002). Despite this significant reduction in plasma glucose concentration, insulin secretion rates (ISRs) increased significantly in IGT subjects (513.3 ± 77.6 vs. 583.1 ± 100.7 pmol/min; P < 0.03), with a trend toward increasing in NIDDM subjects (561.7 ± 122.16 vs. 642.8 ± 128 pmol/min; P = 0.1). These results were compatible with enhanced insulin secretion in the presence of GLP-1. Spectral power was used as a measure of the ability of the β-Cell to secrete insulin in response to small changes in the plasma glucose concentration during the oscillatory infusion. Spectral power for ISR increased from 2.1 ± 0.9 during saline infusion to 7.4 ±1.3 during GLP-1 infusion in IGT subjects (P < 0.004), but was unchanged in NIDDM subjects (1.0 ± 0.4 to 1.5 ± 0.6; P = 0.3). We concluded that low dosage GLP-1 improves the ability of the β-Cell to secrete insulin in both IGT and NIDDM subjects, but that the ability to sense and respond to subtle changes in plasma glucose is improved in IGT subjects, with only a variable response in NIDDM subjects. β-Cell dysfunction was improved by GLP-1 infusion, suggesting that early GLP-1 therapy may preserve β-Cell function in subjects with IGT or mild NIDDM

  • Received September 19, 1997.
  • Revision received April 27, 1998.
  • Accepted April 27, 1998.
  • Copyright © 1998 by the American Diabetes Association
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August 1998, 47(8)
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Glucagon-Like Peptide 1 Improves the Ability of the β-Cell to Sense and Respond to Glucose in Subjects With Impaired Glucose Tolerance
Maria M Byrne, Katja Gliem, Uwe Wank, Rudolf Arnold, Martin Katschinski, Kenneth S Polonsky, Burkhard Goke
Diabetes Aug 1998, 47 (8) 1259-1265; DOI: 10.2337/diab.47.8.1259

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Glucagon-Like Peptide 1 Improves the Ability of the β-Cell to Sense and Respond to Glucose in Subjects With Impaired Glucose Tolerance
Maria M Byrne, Katja Gliem, Uwe Wank, Rudolf Arnold, Martin Katschinski, Kenneth S Polonsky, Burkhard Goke
Diabetes Aug 1998, 47 (8) 1259-1265; DOI: 10.2337/diab.47.8.1259
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