title: Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes.
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: 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.
authors: Mikkel
authors: M
authors: Christensen
authors: 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.
authors: Salvatore
authors: S
authors: Calanna
authors: 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.
authors: Alexander H
authors: AH
authors: Sparre-Ulrich
authors: Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, University of Copenhagen, Hillerød, Denmark.
authors: Peter L
authors: PL
authors: Kristensen
authors: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Mette M
authors: MM
authors: Rosenkilde
authors: Department of Medicine, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
authors: Jens
authors: J
authors: Faber
authors: Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy.
authors: Francesco
authors: F
authors: Purrello
authors: Clinical Metabolomics Core Facility, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Gerrit
authors: G
authors: van Hall
authors: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Jens J
authors: JJ
authors: Holst
authors: Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors: Tina
authors: T
authors: Vilsbøll
authors: 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.
authors: Filip K
authors: FK
authors: Knop
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004357:Drug Synergism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005749:Gastric Inhibitory Polypeptide / Q000008:administration & dosage*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D005990:Glycerol / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005990:Glycerol