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Research article - Peer-reviewed, 2022

Comparative analysis of oral and intraperitoneal glucose tolerance tests in mice

Small, Lewin; Ehrlich, Amy; Iversen, Jo; Ashcroft, Stephen P.; Trost, Kajetan; Moritz, Thomas; Hartmann, Bolette; Holst, Jens J.; Treebak, Jonas T.; Zierath, Juleen R.; Barres, Romain;

Abstract

Objective: The glucose tolerance test (GTT) is widely used in preclinical research to investigate glucose metabolism, but there is no standardised way to administer glucose. The aim of this study was to directly compare the effect of the route of glucose administration on glucose and insulin kinetics during a GTT in mice.Methods: A GTT was performed in lean male and female mice and obese male mice and glucose was administered via the oral or intraperitoneal (I.P.) route. Samples were collected frequently during the GTT to provide a full time-course of the insulin and glucose excursions. In another cohort of lean male mice, plasma concentrations of insulin, c-peptide, and incretin hormones were measured at early time points after glucose administration. A stable-isotope labelled GTT (SiGTT) was then performed to delineate the contribution of exogenous and endogenous glucose to glycemia during the GTT, comparing both methods of glucose administration. Finally, we present a method to easily measure insulin from small volumes of blood during a GTT by directly assaying whole-blood insulin using ELISA and show a good concordance between whole-blood and plasma insulin measurements.Results: We report that I.P. glucose administration results in an elevated blood glucose excursion and a largely absent elevation in blood insulin and plasma incretin hormones when compared to oral administration. Utilising stable-isotope labelled glucose, we demonstrate that the difference in glucose excursion between the two routes of administration is mainly due to the lack of suppression of glucose production in I.P. injected mice. Additionally, rates of exogenous glucose appearance into circulation were different between lean and obese mice after I.P., but not after oral glucose administration.Conclusion: Reflecting on these data, we suggest that careful consideration be given to the route of glucose administration when planning a GTT procedure in mice and that in most circumstances the oral route of glucose administration should be preferred over the I.P. route to avoid possible artifacts originating from a non-physiological route. (c) 2022 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Keywords

Glucose tolerance test; Intraperitoneal; Oral; Mouse; Insulin; Incretin

Published in

Molecular Metabolism

2022, volume: 57, article number: 101440
Publisher: ELSEVIER

Authors' information

Small, Lewin
Novo Nordisk Foundation
Ehrlich, Amy
Novo Nordisk Foundation
Iversen, Jo
Novo Nordisk Foundation
Ashcroft, Stephen
Novo Nordisk Foundation
Trost, Kajetan
Novo Nordisk Foundation
Novo Nordisk Foundation
Swedish University of Agricultural Sciences, Department of Forest Genetics and Plant Physiology
Hartmann, Bolette
Novo Nordisk Foundation
Hartmann, Bolette
University of Copenhagen
Holst, Jens
Novo Nordisk Foundation
Holst, Jens
University of Copenhagen
Treebak, Jonas
Novo Nordisk Foundation
Zierath, Juleen
Novo Nordisk Foundation
Zierath, Juleen R.
Karolinska Institutet
Barres, Romain
Novo Nordisk Foundation
Barres, Romain
Universite Cote d'Azur

UKÄ Subject classification

Endocrinology and Diabetes

Publication Identifiers

DOI: https://doi.org/10.1016/j.molmet.2022.101440

URI (permanent link to this page)

https://res.slu.se/id/publ/117180