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Dissociated effects of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide-1 on beta-cell secretion and insulin clearance in mice

Pacini, Giovanni; Thomaseth, Karl and Ahrén, Bo LU (2010) In Metabolism, Clinical and Experimental 59(7). p.988-992
Abstract
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) potently augment insulin response to glucose. It is less known what their effects are insulin clearance, which also contributes to peripheral hyperinsulinemia observed after administration of incretins together with glucose. The aims of this study were the quantification of C-peptide secretion and the evaluation of insulin clearance after administration of GIP with glucose. This allows the assessment of GIP's effects on hyperinsulinemia. In addition, GIP's effects were compared with those of GLP-1. Anesthetized female NMRI mice were injected intravenously with glucose alone (1 g/kg, n = 35) or glucose together with GIP (50 mu g/kg, n = 12). Samples were... (More)
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) potently augment insulin response to glucose. It is less known what their effects are insulin clearance, which also contributes to peripheral hyperinsulinemia observed after administration of incretins together with glucose. The aims of this study were the quantification of C-peptide secretion and the evaluation of insulin clearance after administration of GIP with glucose. This allows the assessment of GIP's effects on hyperinsulinemia. In addition, GIP's effects were compared with those of GLP-1. Anesthetized female NMRI mice were injected intravenously with glucose alone (1 g/kg, n = 35) or glucose together with GIP (50 mu g/kg, n = 12). Samples were taken through the following 50 minutes, and C-peptide and insulin concentrations were used to reconstruct C-peptide secretion rate and insulin clearance. In a previous study, GLP-1 (10 mu g/kg) was used in 12 mice; and we used those GLP-1 results to compare GIP effects with those of GLP-1. C-peptide secretion rate peaked at 1 minute after glucose injection, and the immediate part of the insulin-releasing process was markedly augmented by both incretin hormones (1-minute suprabasal increment secretory rate was 20 +/- 2 pmol/min for GIP and 28 +/- 2 pmol/min for GLP-1, vs only 9 +/- 1 pmol/min for glucose alone; P < .001). Until 10 minutes after administration, C-peptide secretion remained higher with incretins (P < .0001), whereas starting from 20 minutes, the 3 patterns were undistinguishable (P > .2). Insulin clearance, previously shown to be abridged by 46% with GLP-1, was reduced only by a nonsignificant (P = .27) 21% with GIP. This study thus shows that the 2 incretins markedly augment glucose-stimulated insulin secretion in mice by a preferential action on the immediate response to glucose of insulin secretion. However, the action of GIP is less effective than that of GLP-1. Insulin clearance with GIP is not significantly reduced. We conclude that GIP is less potent than GLP-1 in inducing glucose-stimulated hyperinsulinemia in the mouse. (C) 2010 Elsevier Inc. All rights reserved. (Less)
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publishing date
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Contribution to journal
publication status
published
subject
in
Metabolism, Clinical and Experimental
volume
59
issue
7
pages
988 - 992
publisher
Elsevier
external identifiers
  • wos:000278854400009
  • scopus:77952886782
ISSN
1532-8600
DOI
10.1016/j.metabol.2009.10.021
language
English
LU publication?
yes
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54f50410-0cb2-4af7-b102-e9c3cdd404b2 (old id 1630345)
date added to LUP
2010-07-22 14:10:54
date last changed
2018-05-29 11:15:07
@article{54f50410-0cb2-4af7-b102-e9c3cdd404b2,
  abstract     = {Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) potently augment insulin response to glucose. It is less known what their effects are insulin clearance, which also contributes to peripheral hyperinsulinemia observed after administration of incretins together with glucose. The aims of this study were the quantification of C-peptide secretion and the evaluation of insulin clearance after administration of GIP with glucose. This allows the assessment of GIP's effects on hyperinsulinemia. In addition, GIP's effects were compared with those of GLP-1. Anesthetized female NMRI mice were injected intravenously with glucose alone (1 g/kg, n = 35) or glucose together with GIP (50 mu g/kg, n = 12). Samples were taken through the following 50 minutes, and C-peptide and insulin concentrations were used to reconstruct C-peptide secretion rate and insulin clearance. In a previous study, GLP-1 (10 mu g/kg) was used in 12 mice; and we used those GLP-1 results to compare GIP effects with those of GLP-1. C-peptide secretion rate peaked at 1 minute after glucose injection, and the immediate part of the insulin-releasing process was markedly augmented by both incretin hormones (1-minute suprabasal increment secretory rate was 20 +/- 2 pmol/min for GIP and 28 +/- 2 pmol/min for GLP-1, vs only 9 +/- 1 pmol/min for glucose alone; P &lt; .001). Until 10 minutes after administration, C-peptide secretion remained higher with incretins (P &lt; .0001), whereas starting from 20 minutes, the 3 patterns were undistinguishable (P &gt; .2). Insulin clearance, previously shown to be abridged by 46% with GLP-1, was reduced only by a nonsignificant (P = .27) 21% with GIP. This study thus shows that the 2 incretins markedly augment glucose-stimulated insulin secretion in mice by a preferential action on the immediate response to glucose of insulin secretion. However, the action of GIP is less effective than that of GLP-1. Insulin clearance with GIP is not significantly reduced. We conclude that GIP is less potent than GLP-1 in inducing glucose-stimulated hyperinsulinemia in the mouse. (C) 2010 Elsevier Inc. All rights reserved.},
  author       = {Pacini, Giovanni and Thomaseth, Karl and Ahrén, Bo},
  issn         = {1532-8600},
  language     = {eng},
  number       = {7},
  pages        = {988--992},
  publisher    = {Elsevier},
  series       = {Metabolism, Clinical and Experimental},
  title        = {Dissociated effects of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide-1 on beta-cell secretion and insulin clearance in mice},
  url          = {http://dx.doi.org/10.1016/j.metabol.2009.10.021},
  volume       = {59},
  year         = {2010},
}