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Glucagon-like peptide-1 accelerates the onset of insulin action on glucose disappearance in mice

Thomaseth, K.; Pavan, A.; Pacini, G. and Ahrén, Bo LU (2007) In American Journal of Physiology: Endocrinology and Metabolism 292(6). p.1808-1814
Abstract
Glucagon- like peptide-1 ( GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model... (More)
Glucagon- like peptide-1 ( GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model parameters were estimated from glucose and insulin data collected in 209 anesthetized normal mice after intravenous injection of glucose ( 1 g/ kg) alone or with GLP- 1 ( 0.03 - 100 nmol/ kg). Insulin secretion markedly increased, as expected, with increasing GLP-1 dose. However, minimal model- derived indexes, i. e., insulin sensitivity and glucose effectiveness, did not significantly change with GLP-1 dose. Instead, fractional turnover rate of insulin action [ P-2 = 0.0207 +/- 24.3% ( min) at zero GLP-1 dose] increased steadily with administered GLP-1 dose, with significant differences at 10.4 nmol/ kg ( P-2 = 0.040 +/- 15.5%, P = 0.0046) and 31.2 nmol/ kg ( P-2 = 0.050 +/- 29.2%, P = 0.01). These results show that GLP-1 influences the dynamics of insulin action by accelerating insulin action following glucose challenge. This is a novel mechanism contributing to the glucose- lowering action of GLP-1. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
insulin secretion, insulin sensitivity, glucose kinetics, minimal model, modeling, mathematical
in
American Journal of Physiology: Endocrinology and Metabolism
volume
292
issue
6
pages
1808 - 1814
publisher
American Physiological Society
external identifiers
  • wos:000247939100035
  • scopus:34447556821
ISSN
1522-1555
DOI
10.1152/ajpendo.00303.2006
language
English
LU publication?
yes
id
6b82d350-6957-4784-8560-18b6e3de1703 (old id 647881)
date added to LUP
2007-12-21 14:31:05
date last changed
2017-07-02 04:23:21
@article{6b82d350-6957-4784-8560-18b6e3de1703,
  abstract     = {Glucagon- like peptide-1 ( GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model parameters were estimated from glucose and insulin data collected in 209 anesthetized normal mice after intravenous injection of glucose ( 1 g/ kg) alone or with GLP- 1 ( 0.03 - 100 nmol/ kg). Insulin secretion markedly increased, as expected, with increasing GLP-1 dose. However, minimal model- derived indexes, i. e., insulin sensitivity and glucose effectiveness, did not significantly change with GLP-1 dose. Instead, fractional turnover rate of insulin action [ P-2 = 0.0207 +/- 24.3% ( min) at zero GLP-1 dose] increased steadily with administered GLP-1 dose, with significant differences at 10.4 nmol/ kg ( P-2 = 0.040 +/- 15.5%, P = 0.0046) and 31.2 nmol/ kg ( P-2 = 0.050 +/- 29.2%, P = 0.01). These results show that GLP-1 influences the dynamics of insulin action by accelerating insulin action following glucose challenge. This is a novel mechanism contributing to the glucose- lowering action of GLP-1.},
  author       = {Thomaseth, K. and Pavan, A. and Pacini, G. and Ahrén, Bo},
  issn         = {1522-1555},
  keyword      = {insulin secretion,insulin sensitivity,glucose kinetics,minimal model,modeling,mathematical},
  language     = {eng},
  number       = {6},
  pages        = {1808--1814},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Glucagon-like peptide-1 accelerates the onset of insulin action on glucose disappearance in mice},
  url          = {http://dx.doi.org/10.1152/ajpendo.00303.2006},
  volume       = {292},
  year         = {2007},
}