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Islet adaptation in GIP receptor knockout mice

Ahrén, Bo LU ; Yamada, Yuchiro and Seino, Yutaka (2019) In Peptides
Abstract

Glucose-dependent insulinotropic polypeptide (GIP) receptor knockout (KO) mice are tools for studying GIP physiology. Previous results have demonstrated that these mice have impaired insulin response to oral glucose. In this study, we examined the insulin response to intravenous glucose by measuring glucose, insulin and C-peptide after intravenous glucose (0.35 g/kg) in 5-h fasted female GIP receptor KO mice and their wild-type (WT) littermates. The 1 min insulin and C-peptide responses to intravenous glucose were significantly enhanced in GIP receptor KO mice (n = 26) compared to WT mice (n = 30) as was beta cell function (area under the 50 min C-peptide curve divided by area under the 50 min curve for glucose) (P = 0.001). Beta cell... (More)

Glucose-dependent insulinotropic polypeptide (GIP) receptor knockout (KO) mice are tools for studying GIP physiology. Previous results have demonstrated that these mice have impaired insulin response to oral glucose. In this study, we examined the insulin response to intravenous glucose by measuring glucose, insulin and C-peptide after intravenous glucose (0.35 g/kg) in 5-h fasted female GIP receptor KO mice and their wild-type (WT) littermates. The 1 min insulin and C-peptide responses to intravenous glucose were significantly enhanced in GIP receptor KO mice (n = 26) compared to WT mice (n = 30) as was beta cell function (area under the 50 min C-peptide curve divided by area under the 50 min curve for glucose) (P = 0.001). Beta cell function after intravenous glucose was also enhanced in GIP receptor KO mice in the presence of the glucagon-like peptide-1 receptor antagonist exendin 9 (30 nmol/kg; P = 0.007), the muscarinic antagonist atropine (5 mg/kg; P = 0.007) and the combination of the alpha-adrenoceptor antagonist yohimbine (1.4 mg/kg) and the beta-adrenoceptor antagonist propranolol (2.5 mg/kg; P = 0.042). Analysis of the regression between fasting glucose (6.8 ± 0.1 mmol/l in GIP receptor KO mice and 7.5 ± 0.2 mmol/l in WT mice, P = 0.003) and the 1 min C-peptide response to intravenous glucose showed a negative linear regression between these variables in both WT (n = 60; r = −0.425, P = 0.001) and GIP receptor KO mice (n = 56; r = −0.474, P < 0.001). We conclude that there is a beta cell adaptation in GIP receptor KO mice resulting in enhanced insulin secretion after intravenous glucose to which slight long-term reduction in circulating glucose in these mice may contribute.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adrenergic, Beta cell function, C-peptide, Cholinergic, GIP, GLP-1, Insulin, Knockout mice
in
Peptides
article number
170152
publisher
Elsevier
external identifiers
  • pmid:31522751
  • scopus:85072036261
ISSN
0196-9781
DOI
10.1016/j.peptides.2019.170152
language
English
LU publication?
yes
id
9a2d630a-0bb3-4c40-adff-4e7e4afaf8f5
date added to LUP
2019-09-27 09:51:44
date last changed
2020-07-08 05:04:51
@article{9a2d630a-0bb3-4c40-adff-4e7e4afaf8f5,
  abstract     = {<p>Glucose-dependent insulinotropic polypeptide (GIP) receptor knockout (KO) mice are tools for studying GIP physiology. Previous results have demonstrated that these mice have impaired insulin response to oral glucose. In this study, we examined the insulin response to intravenous glucose by measuring glucose, insulin and C-peptide after intravenous glucose (0.35 g/kg) in 5-h fasted female GIP receptor KO mice and their wild-type (WT) littermates. The 1 min insulin and C-peptide responses to intravenous glucose were significantly enhanced in GIP receptor KO mice (n = 26) compared to WT mice (n = 30) as was beta cell function (area under the 50 min C-peptide curve divided by area under the 50 min curve for glucose) (P = 0.001). Beta cell function after intravenous glucose was also enhanced in GIP receptor KO mice in the presence of the glucagon-like peptide-1 receptor antagonist exendin 9 (30 nmol/kg; P = 0.007), the muscarinic antagonist atropine (5 mg/kg; P = 0.007) and the combination of the alpha-adrenoceptor antagonist yohimbine (1.4 mg/kg) and the beta-adrenoceptor antagonist propranolol (2.5 mg/kg; P = 0.042). Analysis of the regression between fasting glucose (6.8 ± 0.1 mmol/l in GIP receptor KO mice and 7.5 ± 0.2 mmol/l in WT mice, P = 0.003) and the 1 min C-peptide response to intravenous glucose showed a negative linear regression between these variables in both WT (n = 60; r = −0.425, P = 0.001) and GIP receptor KO mice (n = 56; r = −0.474, P &lt; 0.001). We conclude that there is a beta cell adaptation in GIP receptor KO mice resulting in enhanced insulin secretion after intravenous glucose to which slight long-term reduction in circulating glucose in these mice may contribute.</p>},
  author       = {Ahrén, Bo and Yamada, Yuchiro and Seino, Yutaka},
  issn         = {0196-9781},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {Islet adaptation in GIP receptor knockout mice},
  url          = {http://dx.doi.org/10.1016/j.peptides.2019.170152},
  doi          = {10.1016/j.peptides.2019.170152},
  year         = {2019},
}