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Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health

INTRODUCTION: While oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage...

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Autores principales: Wagner, Robert, Eckstein, Sabine S., Fritsche, Louise, Prystupa, Katsiaryna, Hörber, Sebastian, Häring, Hans-Ulrich, Birkenfeld, Andreas L., Peter, Andreas, Fritsche, Andreas, Heni, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297683/
https://www.ncbi.nlm.nih.gov/pubmed/35872982
http://dx.doi.org/10.3389/fendo.2022.892677
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author Wagner, Robert
Eckstein, Sabine S.
Fritsche, Louise
Prystupa, Katsiaryna
Hörber, Sebastian
Häring, Hans-Ulrich
Birkenfeld, Andreas L.
Peter, Andreas
Fritsche, Andreas
Heni, Martin
author_facet Wagner, Robert
Eckstein, Sabine S.
Fritsche, Louise
Prystupa, Katsiaryna
Hörber, Sebastian
Häring, Hans-Ulrich
Birkenfeld, Andreas L.
Peter, Andreas
Fritsche, Andreas
Heni, Martin
author_sort Wagner, Robert
collection PubMed
description INTRODUCTION: While oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health. RESEARCH DESIGN AND METHODS: We used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort. RESULTS: Glucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01). CONCLUSIONS: Glucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype.
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spelling pubmed-92976832022-07-21 Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health Wagner, Robert Eckstein, Sabine S. Fritsche, Louise Prystupa, Katsiaryna Hörber, Sebastian Häring, Hans-Ulrich Birkenfeld, Andreas L. Peter, Andreas Fritsche, Andreas Heni, Martin Front Endocrinol (Lausanne) Endocrinology INTRODUCTION: While oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health. RESEARCH DESIGN AND METHODS: We used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort. RESULTS: Glucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01). CONCLUSIONS: Glucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype. Frontiers Media S.A. 2022-06-29 /pmc/articles/PMC9297683/ /pubmed/35872982 http://dx.doi.org/10.3389/fendo.2022.892677 Text en Copyright © 2022 Wagner, Eckstein, Fritsche, Prystupa, Hörber, Häring, Birkenfeld, Peter, Fritsche and Heni https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Wagner, Robert
Eckstein, Sabine S.
Fritsche, Louise
Prystupa, Katsiaryna
Hörber, Sebastian
Häring, Hans-Ulrich
Birkenfeld, Andreas L.
Peter, Andreas
Fritsche, Andreas
Heni, Martin
Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
title Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
title_full Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
title_fullStr Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
title_full_unstemmed Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
title_short Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health
title_sort postprandial dynamics of proglucagon cleavage products and their relation to metabolic health
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297683/
https://www.ncbi.nlm.nih.gov/pubmed/35872982
http://dx.doi.org/10.3389/fendo.2022.892677
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