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Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice

It has previously been shown that the incretin effect accounts for ≈50% of the insulin response to oral glucose in normal mice. Now, I have proceeded and studied the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) to the insulin response to oral...

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Autor principal: Ahrén, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953110/
https://www.ncbi.nlm.nih.gov/pubmed/36831127
http://dx.doi.org/10.3390/biomedicines11020591
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author Ahrén, Bo
author_facet Ahrén, Bo
author_sort Ahrén, Bo
collection PubMed
description It has previously been shown that the incretin effect accounts for ≈50% of the insulin response to oral glucose in normal mice. Now, I have proceeded and studied the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) to the insulin response to oral glucose in female mice by using receptor antagonists. A specific GIP receptor antagonist (mGIP(3-30); 50 or 500 nmol/kg), a specific GLP-1 receptor antagonist (exendin(9-39); 3 or 30 nmol/kg), the combination of mGIP (500 nmol/kg) and exendin(9-39) (30 nmol/kg), or saline was given intravenously four minutes after administration of glucose (50 mg) through a gastric tube in anesthetized C57/BL6J mice (n = 95) with samples obtained before glucose administration and after 15, 30 and 60 min. The insulinogenic index, determined as the area under the 60 min curve for insulin (AUC(insulin)) divided by the AUC(glucose), was used to reflect the insulin response. It was found that the insulinogenic index was reduced by 67 ± 4% by mGIP(3-30) (p < 0.001), by 60 ± 14% by exendin(9-39) (p = 0.007) and by 61 ± 14% by the combination of mGIP(3-30) and exendin(9-39) (p = 0.043), both at their highest doses, compared to animals injected with glucose in the same experimental series. It is concluded that both GIP and GLP-1 are required for a normal incretin effect in female mice, that they contribute similarly to the insulin response, and that it is unlikely that there is another incretin hormone in this species.
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spelling pubmed-99531102023-02-25 Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice Ahrén, Bo Biomedicines Communication It has previously been shown that the incretin effect accounts for ≈50% of the insulin response to oral glucose in normal mice. Now, I have proceeded and studied the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) to the insulin response to oral glucose in female mice by using receptor antagonists. A specific GIP receptor antagonist (mGIP(3-30); 50 or 500 nmol/kg), a specific GLP-1 receptor antagonist (exendin(9-39); 3 or 30 nmol/kg), the combination of mGIP (500 nmol/kg) and exendin(9-39) (30 nmol/kg), or saline was given intravenously four minutes after administration of glucose (50 mg) through a gastric tube in anesthetized C57/BL6J mice (n = 95) with samples obtained before glucose administration and after 15, 30 and 60 min. The insulinogenic index, determined as the area under the 60 min curve for insulin (AUC(insulin)) divided by the AUC(glucose), was used to reflect the insulin response. It was found that the insulinogenic index was reduced by 67 ± 4% by mGIP(3-30) (p < 0.001), by 60 ± 14% by exendin(9-39) (p = 0.007) and by 61 ± 14% by the combination of mGIP(3-30) and exendin(9-39) (p = 0.043), both at their highest doses, compared to animals injected with glucose in the same experimental series. It is concluded that both GIP and GLP-1 are required for a normal incretin effect in female mice, that they contribute similarly to the insulin response, and that it is unlikely that there is another incretin hormone in this species. MDPI 2023-02-16 /pmc/articles/PMC9953110/ /pubmed/36831127 http://dx.doi.org/10.3390/biomedicines11020591 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Ahrén, Bo
Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice
title Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice
title_full Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice
title_fullStr Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice
title_full_unstemmed Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice
title_short Contribution of GIP and GLP-1 to the Insulin Response to Oral Administration of Glucose in Female Mice
title_sort contribution of gip and glp-1 to the insulin response to oral administration of glucose in female mice
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953110/
https://www.ncbi.nlm.nih.gov/pubmed/36831127
http://dx.doi.org/10.3390/biomedicines11020591
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