Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice
(2011) In American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 300(5). p.1126-1133- Abstract
- Chan HM, Jain R, Ahren B, Pacini G, D'Argenio DZ. Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice. Am J Physiol Regul Integr Comp Physiol 300: R1126-R1133, 2011. First published February 9, 2010; doi:10.1152/ajpregu.00687.2010.-The increase in insulin secretion caused by glucagon-like peptide-1 (GLP-1) and GLP-1 mimetics observed during an intravenous glucose test (IVGTT) has been reported in both normal and disease animal models, as well as in humans. In this study, a hierarchical population modeling approach is used, together with a previously reported model relating glucose to insulin appearance, to determine quantitative in vivo dose-response... (More)
- Chan HM, Jain R, Ahren B, Pacini G, D'Argenio DZ. Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice. Am J Physiol Regul Integr Comp Physiol 300: R1126-R1133, 2011. First published February 9, 2010; doi:10.1152/ajpregu.00687.2010.-The increase in insulin secretion caused by glucagon-like peptide-1 (GLP-1) and GLP-1 mimetics observed during an intravenous glucose test (IVGTT) has been reported in both normal and disease animal models, as well as in humans. In this study, a hierarchical population modeling approach is used, together with a previously reported model relating glucose to insulin appearance, to determine quantitative in vivo dose-response relationships between GLP-1 dose level and both first-and second-phase insulin release. Parameters of the insulin kinetic model were estimated from the complete set of glucose and insulin data collected in 219 anesthetized nonfasted NMR-imaged mice after intravenous injection of glucose (1 g/kg) alone or with GLP-1 (0.03-100 nmol/kg). The resulting dose-response curves indicate a difference in GLP-1 effect on the two release phases, as is also evident from the different ED50 parameter values (0.107 vs. 6.65 nmol/kg for phase 1 vs. phase 2 insulin release parameters). The first phase of insulin release is gradually augmented with increasing GLP-1 dose, reaching saturation at a dose of similar to 1 nmol/kg, while the second-phase release changes more abruptly at GLP-1 doses between 3 and 10 nmol/kg and shows a more pronounced 100-fold increase between control and the high GLP-1 dose of 100 nmol/kg Moreover, separate disposition indices calculated for phase 1 and 2 insulin release, show a different pattern of increase with increasing GLP-1 dose. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1988169
- author
- Chan, Hui Min ; Jain, Ritesh ; Ahrén, Bo LU ; Pacini, Giovanni and D'Argenio, David Z.
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- glucose tolerance, insulin secretion, insulin sensitivity, intravenous, glucose test, population analysis
- in
- American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
- volume
- 300
- issue
- 5
- pages
- 1126 - 1133
- publisher
- American Physiological Society
- external identifiers
-
- wos:000290149800010
- scopus:79955754193
- pmid:21307364
- ISSN
- 0363-6119
- DOI
- 10.1152/ajpregu.00687.2010
- language
- English
- LU publication?
- yes
- id
- a72fe7a2-1a9d-4d12-a154-28eff3a5d9b9 (old id 1988169)
- date added to LUP
- 2016-04-01 14:01:04
- date last changed
- 2025-04-04 15:15:41
@article{a72fe7a2-1a9d-4d12-a154-28eff3a5d9b9,
abstract = {{Chan HM, Jain R, Ahren B, Pacini G, D'Argenio DZ. Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice. Am J Physiol Regul Integr Comp Physiol 300: R1126-R1133, 2011. First published February 9, 2010; doi:10.1152/ajpregu.00687.2010.-The increase in insulin secretion caused by glucagon-like peptide-1 (GLP-1) and GLP-1 mimetics observed during an intravenous glucose test (IVGTT) has been reported in both normal and disease animal models, as well as in humans. In this study, a hierarchical population modeling approach is used, together with a previously reported model relating glucose to insulin appearance, to determine quantitative in vivo dose-response relationships between GLP-1 dose level and both first-and second-phase insulin release. Parameters of the insulin kinetic model were estimated from the complete set of glucose and insulin data collected in 219 anesthetized nonfasted NMR-imaged mice after intravenous injection of glucose (1 g/kg) alone or with GLP-1 (0.03-100 nmol/kg). The resulting dose-response curves indicate a difference in GLP-1 effect on the two release phases, as is also evident from the different ED50 parameter values (0.107 vs. 6.65 nmol/kg for phase 1 vs. phase 2 insulin release parameters). The first phase of insulin release is gradually augmented with increasing GLP-1 dose, reaching saturation at a dose of similar to 1 nmol/kg, while the second-phase release changes more abruptly at GLP-1 doses between 3 and 10 nmol/kg and shows a more pronounced 100-fold increase between control and the high GLP-1 dose of 100 nmol/kg Moreover, separate disposition indices calculated for phase 1 and 2 insulin release, show a different pattern of increase with increasing GLP-1 dose.}},
author = {{Chan, Hui Min and Jain, Ritesh and Ahrén, Bo and Pacini, Giovanni and D'Argenio, David Z.}},
issn = {{0363-6119}},
keywords = {{glucose tolerance; insulin secretion; insulin sensitivity; intravenous; glucose test; population analysis}},
language = {{eng}},
number = {{5}},
pages = {{1126--1133}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology: Regulatory, Integrative and Comparative Physiology}},
title = {{Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice}},
url = {{http://dx.doi.org/10.1152/ajpregu.00687.2010}},
doi = {{10.1152/ajpregu.00687.2010}},
volume = {{300}},
year = {{2011}},
}