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Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes.
Diabetes. 2015 Jan; 64(1):72-8.D

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/m(2), 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.

Authors+Show Affiliations

Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark mch@dadlnet.dk.Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy.Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, University of Copenhagen, Hillerød, Denmark.Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Medicine, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy.Clinical Metabolomics Core Facility, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

25053587

Citation

Christensen, Mikkel, et al. "Glucose-dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes." Diabetes, vol. 64, no. 1, 2015, pp. 72-8.
Christensen M, Calanna S, Sparre-Ulrich AH, et al. Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. Diabetes. 2015;64(1):72-8.
Christensen, M., Calanna, S., Sparre-Ulrich, A. H., Kristensen, P. L., Rosenkilde, M. M., Faber, J., Purrello, F., van Hall, G., Holst, J. J., Vilsbøll, T., & Knop, F. K. (2015). Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. Diabetes, 64(1), 72-8. https://doi.org/10.2337/db14-0440
Christensen M, et al. Glucose-dependent Insulinotropic Polypeptide Augments Glucagon Responses to Hypoglycemia in Type 1 Diabetes. Diabetes. 2015;64(1):72-8. PubMed PMID: 25053587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes. AU - Christensen,Mikkel, AU - Calanna,Salvatore, AU - Sparre-Ulrich,Alexander H, AU - Kristensen,Peter L, AU - Rosenkilde,Mette M, AU - Faber,Jens, AU - Purrello,Francesco, AU - van Hall,Gerrit, AU - Holst,Jens J, AU - Vilsbøll,Tina, AU - Knop,Filip K, Y1 - 2014/07/22/ PY - 2014/7/24/entrez PY - 2014/7/24/pubmed PY - 2015/3/12/medline SP - 72 EP - 8 JF - Diabetes JO - Diabetes VL - 64 IS - 1 N2 - 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/m(2), 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. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/25053587/Glucose_dependent_insulinotropic_polypeptide_augments_glucagon_responses_to_hypoglycemia_in_type_1_diabetes_ DB - PRIME DP - Unbound Medicine ER -