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Glucagon increases insulin levels by stimulating insulin secretion without effect on insulin clearance in mice

Song, Gina; Pacini, Giovanni; Ahrén, Bo LU and D'Argenio, David Z. (2017) In Peptides 88. p.74-79
Abstract

Circulating insulin is dependent on a balance between insulin appearance through secretion and insulin clearance. However, to what extent changes in insulin clearance contribute to the increased insulin levels after glucagon administration is not known. This study therefore assessed and quantified any potential effect of glucagon on insulin kinetics in mice. Prehepatic insulin secretion in mice was first estimated following glucose (0.35 g/kg i.v.) and following glucose plus glucagon (10 μg/kg i.v.) using deconvolution of plasma C-peptide concentrations. Plasma concentrations of glucose, insulin, and glucagon were then measured simultaneously in individual mice following glucose alone or glucose plus glucagon (pre dose and at 1, 5, 10,... (More)

Circulating insulin is dependent on a balance between insulin appearance through secretion and insulin clearance. However, to what extent changes in insulin clearance contribute to the increased insulin levels after glucagon administration is not known. This study therefore assessed and quantified any potential effect of glucagon on insulin kinetics in mice. Prehepatic insulin secretion in mice was first estimated following glucose (0.35 g/kg i.v.) and following glucose plus glucagon (10 μg/kg i.v.) using deconvolution of plasma C-peptide concentrations. Plasma concentrations of glucose, insulin, and glucagon were then measured simultaneously in individual mice following glucose alone or glucose plus glucagon (pre dose and at 1, 5, 10, 20 min post). Using the previously determined insulin secretion profiles and the insulin concentration-time measurements, a population modeling analysis was applied to estimate the one-compartment kinetics of insulin disposition with and without glucagon. Glucagon with glucose significantly enhanced prehepatic insulin secretion (Cmax and AUC0-20) compared to that with glucose alone (p < 0.0001). From the modeling analysis, the population mean and between-animal SD of insulin clearance was 6.4 ± 0.34 mL/min for glucose alone and 5.8 ± 1.5 mL/min for glucagon plus glucose, with no significant effect of glucagon on mean insulin clearance. Therefore, we conclude that the enhancement of circulating insulin after glucagon administration is solely due to stimulated insulin secretion.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glucagon, Insulin clearance, Insulin secretion, Population analysis
in
Peptides
volume
88
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85007405309
  • wos:000393930700010
ISSN
0196-9781
DOI
10.1016/j.peptides.2016.12.012
language
English
LU publication?
yes
id
eabecee0-0e04-4f77-bd62-a08bddfacdcd
date added to LUP
2017-02-03 13:40:41
date last changed
2017-09-18 11:36:23
@article{eabecee0-0e04-4f77-bd62-a08bddfacdcd,
  abstract     = {<p>Circulating insulin is dependent on a balance between insulin appearance through secretion and insulin clearance. However, to what extent changes in insulin clearance contribute to the increased insulin levels after glucagon administration is not known. This study therefore assessed and quantified any potential effect of glucagon on insulin kinetics in mice. Prehepatic insulin secretion in mice was first estimated following glucose (0.35 g/kg i.v.) and following glucose plus glucagon (10 μg/kg i.v.) using deconvolution of plasma C-peptide concentrations. Plasma concentrations of glucose, insulin, and glucagon were then measured simultaneously in individual mice following glucose alone or glucose plus glucagon (pre dose and at 1, 5, 10, 20 min post). Using the previously determined insulin secretion profiles and the insulin concentration-time measurements, a population modeling analysis was applied to estimate the one-compartment kinetics of insulin disposition with and without glucagon. Glucagon with glucose significantly enhanced prehepatic insulin secretion (Cmax and AUC<sub>0-20</sub>) compared to that with glucose alone (p &lt; 0.0001). From the modeling analysis, the population mean and between-animal SD of insulin clearance was 6.4 ± 0.34 mL/min for glucose alone and 5.8 ± 1.5 mL/min for glucagon plus glucose, with no significant effect of glucagon on mean insulin clearance. Therefore, we conclude that the enhancement of circulating insulin after glucagon administration is solely due to stimulated insulin secretion.</p>},
  author       = {Song, Gina and Pacini, Giovanni and Ahrén, Bo and D'Argenio, David Z.},
  issn         = {0196-9781},
  keyword      = {Glucagon,Insulin clearance,Insulin secretion,Population analysis},
  language     = {eng},
  month        = {02},
  pages        = {74--79},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {Glucagon increases insulin levels by stimulating insulin secretion without effect on insulin clearance in mice},
  url          = {http://dx.doi.org/10.1016/j.peptides.2016.12.012},
  volume       = {88},
  year         = {2017},
}