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

TY - JOUR

T1 - Mathematical Modelling of Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide-1 following Ingestion of Glucose

AU - Røge, Rikke M

AU - Bagger, Jonatan I

AU - Alskär, Oskar

AU - Kristensen, Niels R

AU - Klim, Søren

AU - Holst, Jens J

AU - Ingwersen, Steen H

AU - Karlsson, Mats O

AU - Knop, Filip K

AU - Vilsbøll, Tina

AU - Kjellsson, Maria C

N1 - © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1111/bcpt.12792

DO - 10.1111/bcpt.12792

M3 - Journal article

C2 - 28374974

SN - 1742-7835

VL - 121

SP - 290

EP - 297

JO - Basic and Clinical Pharmacology and Toxicology

JF - Basic and Clinical Pharmacology and Toxicology

IS - 4

ER -