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Glucagon-like peptide-1 and glucose-dependent insulinotropic peptide : effects alone and in combination on insulin secretion and glucose disappearance in mice

Pacini, Giovanni and Ahrén, Bo LU (2017) In Physiological Reports 5(11).
Abstract

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) stimulate insulin secretion. They are both released after meal ingestion, and therefore they might cooperate in their actions. However, whether there is a cooperative action of the two incretins is not known. This study therefore investigated the effects on insulin secretion and glucose disappearance of GLP-1 and GIP when given together with intravenous glucose both alone and in combination in mice. Four different doses were used (0.003, 0.03, 0.3 and 3.0 nmol/kg), which ranged from subthreshold to maximal doses to stimulate first-phase insulin secretion as evident from initial dose–response studies. It was found that at 0.03 nmol/kg and higher doses,... (More)

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) stimulate insulin secretion. They are both released after meal ingestion, and therefore they might cooperate in their actions. However, whether there is a cooperative action of the two incretins is not known. This study therefore investigated the effects on insulin secretion and glucose disappearance of GLP-1 and GIP when given together with intravenous glucose both alone and in combination in mice. Four different doses were used (0.003, 0.03, 0.3 and 3.0 nmol/kg), which ranged from subthreshold to maximal doses to stimulate first-phase insulin secretion as evident from initial dose–response studies. It was found that at 0.03 nmol/kg and higher doses, glucose-stimulated insulin secretion was augmented by both incretins. When they were given in combination, no further increase was observed, indicating no synergistic effect. Also, glucose disappearance rate was increased by 0.03 and 3.0 nmol/kg of the two incretins, both when they were given alone and in combination with, again, no synergy. Finally, glucose effectiveness (an index of noninsulin-mediated processes) was enhanced by the two incretins, in particular GIP. We also found that insulin-dependent and insulin-independent mechanisms contributed 38% and 62%, respectively, to glucose tolerance after glucose alone; with GIP, the contribution by noninsulin-dependent processes was remarkably dominant and with GLP-1, insulin-dependent processes were prevailing. In conclusion, GIP and GLP-1 stimulate insulin secretion and glucose effectiveness in mice with no synergistic action, but with a dissociated contributory effector on glucose disposal: with GLP-1 being more active on insulin-dependent processes and GIP more active on noninsulin-dependent processes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Beta cell function, glucose effectiveness, incretin hormones, insulin sensitivity, intravenous glucose test, mathematical modeling
in
Physiological Reports
volume
5
issue
11
publisher
John Wiley & Sons
external identifiers
  • scopus:85020813454
  • wos:000403500600007
ISSN
2051-817X
DOI
10.14814/phy2.13280
language
English
LU publication?
yes
id
425e1855-9208-42a8-8717-9fb7c8aa2a4b
date added to LUP
2017-07-28 13:15:21
date last changed
2018-01-07 12:13:29
@article{425e1855-9208-42a8-8717-9fb7c8aa2a4b,
  abstract     = {<p>Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) stimulate insulin secretion. They are both released after meal ingestion, and therefore they might cooperate in their actions. However, whether there is a cooperative action of the two incretins is not known. This study therefore investigated the effects on insulin secretion and glucose disappearance of GLP-1 and GIP when given together with intravenous glucose both alone and in combination in mice. Four different doses were used (0.003, 0.03, 0.3 and 3.0 nmol/kg), which ranged from subthreshold to maximal doses to stimulate first-phase insulin secretion as evident from initial dose–response studies. It was found that at 0.03 nmol/kg and higher doses, glucose-stimulated insulin secretion was augmented by both incretins. When they were given in combination, no further increase was observed, indicating no synergistic effect. Also, glucose disappearance rate was increased by 0.03 and 3.0 nmol/kg of the two incretins, both when they were given alone and in combination with, again, no synergy. Finally, glucose effectiveness (an index of noninsulin-mediated processes) was enhanced by the two incretins, in particular GIP. We also found that insulin-dependent and insulin-independent mechanisms contributed 38% and 62%, respectively, to glucose tolerance after glucose alone; with GIP, the contribution by noninsulin-dependent processes was remarkably dominant and with GLP-1, insulin-dependent processes were prevailing. In conclusion, GIP and GLP-1 stimulate insulin secretion and glucose effectiveness in mice with no synergistic action, but with a dissociated contributory effector on glucose disposal: with GLP-1 being more active on insulin-dependent processes and GIP more active on noninsulin-dependent processes.</p>},
  articleno    = {e13280},
  author       = {Pacini, Giovanni and Ahrén, Bo},
  issn         = {2051-817X},
  keyword      = {Beta cell function,glucose effectiveness,incretin hormones,insulin sensitivity,intravenous glucose test,mathematical modeling},
  language     = {eng},
  number       = {11},
  publisher    = {John Wiley & Sons},
  series       = {Physiological Reports},
  title        = {Glucagon-like peptide-1 and glucose-dependent insulinotropic peptide : effects alone and in combination on insulin secretion and glucose disappearance in mice},
  url          = {http://dx.doi.org/10.14814/phy2.13280},
  volume       = {5},
  year         = {2017},
}