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Metabolism

Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes

  1. Mikkel Christensen1,2⇑,
  2. Salvatore Calanna1,3,
  3. Alexander H. Sparre-Ulrich1,4,
  4. Peter L. Kristensen5,
  5. Mette M. Rosenkilde4,
  6. Jens Faber6,
  7. Francesco Purrello3,
  8. Gerrit van Hall7,
  9. Jens J. Holst2,
  10. Tina Vilsbøll1 and
  11. Filip K. Knop1,2
  1. 1Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
  2. 2Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  3. 3Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy
  4. 4Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, University of Copenhagen, Hillerød, Denmark
  6. 6Department of Medicine, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
  7. 7Clinical Metabolomics Core Facility, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  1. Corresponding author: Mikkel Christensen, mch{at}dadlnet.dk.
  1. M.C. and S.C. contributed equally to this study.

Diabetes 2015 Jan; 64(1): 72-78. https://doi.org/10.2337/db14-0440
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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is glucagonotropic, and glucagon-like peptide-1 (GLP-1) is glucagonostatic. We studied the effects of GIP and GLP-1 on glucagon responses to insulin-induced hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Ten male subjects with T1DM (C-peptide negative, age [mean ± SEM] 26 ± 1 years, BMI 24 ± 0.5 kg/m2, HbA1c 7.3 ± 0.2%) were studied in a randomized, double-blinded, crossover study, with 2-h intravenous administration of saline, GIP, or GLP-1. The first hour, plasma glucose was lowered by insulin infusion, and the second hour constituted a “recovery phase.” During the recovery phase, GIP infusions elicited larger glucagon responses (164 ± 50 [GIP] vs. 23 ± 25 [GLP-1] vs. 17 ± 46 [saline] min ⋅ pmol/L, P < 0.03) and endogenous glucose production was higher with GIP and lower with GLP-1 compared with saline (P < 0.02). On the GIP days, significantly less exogenous glucose was needed to keep plasma glucose above 2 mmol/L (155 ± 36 [GIP] vs. 232 ± 40 [GLP-1] vs. 212 ± 56 [saline] mg ⋅ kg−1, P < 0.05). Levels of insulin, cortisol, growth hormone, and noradrenaline, as well as hypoglycemic symptoms and cognitive function, were similar on all days. Our results suggest that during hypoglycemia in patients with T1DM, exogenous GIP increases glucagon responses during the recovery phase after hypoglycemia and reduces the need for glucose administration.

  • Received March 18, 2014.
  • Accepted July 14, 2014.
  • © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes
Mikkel Christensen, Salvatore Calanna, Alexander H. Sparre-Ulrich, Peter L. Kristensen, Mette M. Rosenkilde, Jens Faber, Francesco Purrello, Gerrit van Hall, Jens J. Holst, Tina Vilsbøll, Filip K. Knop
Diabetes Jan 2015, 64 (1) 72-78; DOI: 10.2337/db14-0440

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Glucose-Dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes
Mikkel Christensen, Salvatore Calanna, Alexander H. Sparre-Ulrich, Peter L. Kristensen, Mette M. Rosenkilde, Jens Faber, Francesco Purrello, Gerrit van Hall, Jens J. Holst, Tina Vilsbøll, Filip K. Knop
Diabetes Jan 2015, 64 (1) 72-78; DOI: 10.2337/db14-0440
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