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Glucagon and GLP-1 exhibit no synergistic enhancement of glucose-stimulated insulin secretion in mice.

Pacini, Giovanni and Ahrén, Bo LU (2015) In Peptides 71(Jun 26). p.66-71
Abstract
The combination of glucagon and glucagon-like peptide-1 (GLP-1) has been suggested as an approach to target obesity, since the two hormones have complementary action on body weight. We examined whether complementary action of the two hormones also exist on insulin secretion. Female C57BL/6 mice were injected intravenously with glucose with or without GLP-1, glucagon or the combination of GLP-1 and glucagon at three different dose levels. Furthermore, freshly isolated mouse islets were incubated for 30min in with the presence of 2.8, 11.1 or 16.7mmol/l glucose or with 11.1mmol/l glucose in the presence of 100 nmol/l glucagon and/or GLP-1. It was found that at 1min after glucose injection alone, insulin rose to a peak level and this peak, as... (More)
The combination of glucagon and glucagon-like peptide-1 (GLP-1) has been suggested as an approach to target obesity, since the two hormones have complementary action on body weight. We examined whether complementary action of the two hormones also exist on insulin secretion. Female C57BL/6 mice were injected intravenously with glucose with or without GLP-1, glucagon or the combination of GLP-1 and glucagon at three different dose levels. Furthermore, freshly isolated mouse islets were incubated for 30min in with the presence of 2.8, 11.1 or 16.7mmol/l glucose or with 11.1mmol/l glucose in the presence of 100 nmol/l glucagon and/or GLP-1. It was found that at 1min after glucose injection alone, insulin rose to a peak level and this peak, as well as the 50min area under the insulin curve (AUC insulin) were dose-dependently augmented by GLP-1 and glucagon. However, peak insulin with the two hormones together (with glucose) was not higher than after either single administration at any of the tested doses, i.e., no additive of synergistic action was observed by the combination on glucose-stimulated insulin secretion. Similar results were observed when calculating insulin for the whole test period. Also in vitro, both glucagon and GLP-1 augmented insulin secretion; however, there was no difference between the combined stimulation of insulin secretion by GLP-1 and glucagon together compared with either hormone alone. Insulin sensitivity did not exhibit significant changes from the glucose only condition. We conclude that the acute combined administration of the strongly insulinotropic GLP-1 and glucagon, both in vivo and in vitro, did not induce any additive or synergistic action on glucose-stimulated insulin secretion. This shows that the risk of a marked insulinotropic action when the two compounds are given together most likely does not result in increased risk of hypoglycemia. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Peptides
volume
71
issue
Jun 26
pages
66 - 71
publisher
Elsevier
external identifiers
  • pmid:26119909
  • wos:000361837800009
  • scopus:84937540687
ISSN
1873-5169
DOI
10.1016/j.peptides.2015.05.010
language
English
LU publication?
yes
id
80154c51-d0fc-4c33-8d83-fe30ed7cdc89 (old id 7477532)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26119909?dopt=Abstract
date added to LUP
2015-07-11 09:47:05
date last changed
2017-07-02 03:24:28
@article{80154c51-d0fc-4c33-8d83-fe30ed7cdc89,
  abstract     = {The combination of glucagon and glucagon-like peptide-1 (GLP-1) has been suggested as an approach to target obesity, since the two hormones have complementary action on body weight. We examined whether complementary action of the two hormones also exist on insulin secretion. Female C57BL/6 mice were injected intravenously with glucose with or without GLP-1, glucagon or the combination of GLP-1 and glucagon at three different dose levels. Furthermore, freshly isolated mouse islets were incubated for 30min in with the presence of 2.8, 11.1 or 16.7mmol/l glucose or with 11.1mmol/l glucose in the presence of 100 nmol/l glucagon and/or GLP-1. It was found that at 1min after glucose injection alone, insulin rose to a peak level and this peak, as well as the 50min area under the insulin curve (AUC insulin) were dose-dependently augmented by GLP-1 and glucagon. However, peak insulin with the two hormones together (with glucose) was not higher than after either single administration at any of the tested doses, i.e., no additive of synergistic action was observed by the combination on glucose-stimulated insulin secretion. Similar results were observed when calculating insulin for the whole test period. Also in vitro, both glucagon and GLP-1 augmented insulin secretion; however, there was no difference between the combined stimulation of insulin secretion by GLP-1 and glucagon together compared with either hormone alone. Insulin sensitivity did not exhibit significant changes from the glucose only condition. We conclude that the acute combined administration of the strongly insulinotropic GLP-1 and glucagon, both in vivo and in vitro, did not induce any additive or synergistic action on glucose-stimulated insulin secretion. This shows that the risk of a marked insulinotropic action when the two compounds are given together most likely does not result in increased risk of hypoglycemia.},
  author       = {Pacini, Giovanni and Ahrén, Bo},
  issn         = {1873-5169},
  language     = {eng},
  number       = {Jun 26},
  pages        = {66--71},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {Glucagon and GLP-1 exhibit no synergistic enhancement of glucose-stimulated insulin secretion in mice.},
  url          = {http://dx.doi.org/10.1016/j.peptides.2015.05.010},
  volume       = {71},
  year         = {2015},
}