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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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    Figure 1

    Plasma glucose and hormones. Plasma/serum glucose (A), intact GIP (B), total GLP-1 (C), insulin (D), and glucagon (E) during insulin-induced hypoglycemia with intravenous infusion of GIP (red diamonds), GLP-1 (blue hexagons), or saline (white squares). Data are means ± SEM. Cumulated glucose infusions are depicted as bar graphs (A). Statistical analyses were done with repeated-measures ANOVA; adifferences over time, bdifferences between the groups, abdifferences owing to interaction between group and time. Posttests at individual time points were by Holm-Šídák multiple comparisons tests. Significant differences are indicated by asterisks: *P < 0.05, **P = 0.001 to 0.01, ****P < 0.0001.

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    Figure 2

    Glucose kinetics. Ra (A), glucose Rd (B), rate of endogenous glucose production (C), and glucose infusion rate in 15-min intervals (D) during insulin-induced hypoglycemia with intravenous infusion of GIP (red diamonds), GLP-1 (blue hexagons), or saline (white squares). Data are means ± SEM. Statistical analyses were done with repeated-measures ANOVA; adifferences over time, bdifferences between the groups, abdifferences owing to interaction between group and time. Posttests at individual time points were by Holm-Šídák multiple comparisons tests. Significant differences are indicated by asterisks: *P < 0.05, **P = 0.001–0.01, ***P = 0.0001–0.001.

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    Figure 3

    Serum FFAs and glycerol kinetics. Plasma/serum FFAs (A), glycerol (B), glycerol Ra (C), and glycerol Rd (D) during insulin-induced hypoglycemia with intravenous infusion of GIP (red diamonds), GLP-1 (blue hexagons), or saline (white squares). Data are means ± SEM. Statistical analyses were done with repeated-measures ANOVA; adifferences over time, bdifferences between the groups, abdifferences owing to interaction between group and time. Posttests at individual time points were by Holm-Šídák multiple comparisons tests. *Significant (P < 0.05) difference.

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    Figure 4

    Hypoglycemia symptoms and cognitive function score. Hypoglycemia symptom scores (A) and cognitive function scores (B) depicted as the difference between baseline (time −60 min) and hypoglycemia (time 65 min) during infusion of GIP (red), GLP-1 (blue), or saline (white). Hypoglycemia symptoms were graded using the Edinburgh Hypoglycemia Scale, which is a Likert scale of symptom scores from 1 (not present) to 7 (very intense). Cognitive functions scores are based on the Trail Making Test, which measures time to finish in seconds (B [left y-axis]), and the Stroop test, which measures items named during a 45-s period (B [right y-axis]). Results are depicted as box and whiskers (minimum to maximum). No significant differences between study days were observed.

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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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