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Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice

Chan, Hui Min; Jain, Ritesh; Ahrén, Bo LU ; Pacini, Giovanni and D'Argenio, David Z. (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)
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author
organization
publishing date
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
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
2011-07-01 09:30:12
date last changed
2017-10-08 03:57:51
@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},
  keyword      = {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},
  volume       = {300},
  year         = {2011},
}