Istituto di Ingegneria Biomedica     
Thomaseth K., Pavan A., Pacini G., Ahren B. Glucagon-like peptide-1 (GLP-1) accelerates the onset of insulin action on glucose disappearance in mice. In: American Journal of Physiology-Endocrinology and Metabolism, vol. 292 (6) pp. E1808 - 14. American Physiological Society, 2007.
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 [P2 = 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 (P2 = 0.040 +/- 15.5%, P = 0.0046) and 31.2 nmol/kg (P2 = 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.
URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17311896
DOI: 10.1152/ajpendo.00303.2006
Subject glucose kinetics
Insulin secretion
insulin sensitivity
mathematical modelling
minimal model

Icona documento 1) Download Document PDF

Icona documento Open access Icona documento Restricted Icona documento Private


Per ulteriori informazioni, contattare: Librarian http://puma.isti.cnr.it

Valid HTML 4.0 Transitional