title: Mathematical Modelling of Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide-1 following Ingestion of Glucose.
abstract: The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), play an important role in glucose homeostasis by potentiating glucose-induced insulin secretion. Furthermore, GLP-1 has been reported to play a role in glucose homeostasis by inhibiting glucagon secretion and delaying gastric emptying. As the insulinotropic effect of GLP-1 is preserved in patients with type 2 diabetes (T2D), therapies based on GLP-1 have been developed in recent years, and these have proven to be efficient in the treatment of T2D. The endogenous secretion of both GIP and GLP-1 is stimulated by glucose in the small intestine, and the release is dependent on the amount. In this work, we developed a semimechanistic model describing the release of GIP and GLP-1 after ingestion of various glucose doses in healthy volunteers and patients with T2D. In the model, the release of both hormones is stimulated by glucose in the proximal small intestine, and no differences in the secretion dynamics between healthy individuals and patients with T2D were identified after taking differences in glucose profiles into account.
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.|Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Rikke M
authors.initials: RM
authors.lastname: Røge
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Alskär
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Niels R
authors.initials: NR
authors.lastname: Kristensen
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Klim
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Steen H
authors.initials: SH
authors.lastname: Ingwersen
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mats O
authors.initials: MO
authors.lastname: Karlsson
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Kjellsson
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D005746:Gastric Emptying; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results
chemical_list: D006727:Hormone Antagonists; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005947:Glucose