Mathematical Modelling of Glucose‐Dependent Insulinotropic Polypeptide and Glucagon‐like Peptide‐1 following Ingestion of Glucose

• Published in: Basic & clinical pharmacology & toxicology 2017-10, Vol.121 (4), p.290-297
• Main Authors: Røge, Rikke M., Bagger, Jonatan I., Alskär, Oskar, Kristensen, Niels R., Klim, Søren, Holst, Jens J., Ingwersen, Steen H., Karlsson, Mats O., Knop, Filip K., Vilsbøll, Tina, Kjellsson, Maria C.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Case-Control Studies; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - metabolism; Female; Gastric Emptying; Gastric Inhibitory Polypeptide - metabolism; Gastric Inhibitory Polypeptide - secretion; GIP protein; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - antagonists & inhibitors; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide 1 - secretion; Glucose; Glucose - administration & dosage; Glucose - metabolism; Glucose Tolerance Test; Homeostasis; Hormone Antagonists - pharmacology; Hormones; Humans; Ingestion; Insulin; Insulin secretion; Intestinal Absorption; Intestine; Intestine, Small - drug effects; Intestine, Small - metabolism; Intestine, Small - secretion; Kinetics; Male; Mathematical models; Middle Aged; Models, Biological; Polypeptides; Reproducibility of Results; Secretion; Small intestine
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.12792

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.