Glucagon-like peptide-1 accelerates the onset of insulin action on glucose disappearance in mice
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/647881
- author
- Thomaseth, K. ; Pavan, A. ; Pacini, G. and Ahrén, Bo LU
- organization
- publishing date
- 2007
- 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
- 2016-04-01 16:22:19
- date last changed
- 2024-01-11 06:47:37
@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}},
keywords = {{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}},
doi = {{10.1152/ajpendo.00303.2006}},
volume = {{292}},
year = {{2007}},
}