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Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring

Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia...

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Autores principales: Renner, Simone, Martins, Ana Sofia, Streckel, Elisabeth, Braun-Reichhart, Christina, Backman, Mattias, Prehn, Cornelia, Klymiuk, Nikolai, Bähr, Andrea, Blutke, Andreas, Landbrecht-Schessl, Christina, Wünsch, Annegret, Kessler, Barbara, Kurome, Mayuko, Hinrichs, Arne, Koopmans, Sietse-Jan, Krebs, Stefan, Kemter, Elisabeth, Rathkolb, Birgit, Nagashima, Hiroshi, Blum, Helmut, Ritzmann, Mathias, Wanke, Rüdiger, Aigner, Bernhard, Adamski, Jerzy, Hrabě de Angelis, Martin, Wolf, Eckhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737953/
https://www.ncbi.nlm.nih.gov/pubmed/31308048
http://dx.doi.org/10.1242/dmm.039156
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author Renner, Simone
Martins, Ana Sofia
Streckel, Elisabeth
Braun-Reichhart, Christina
Backman, Mattias
Prehn, Cornelia
Klymiuk, Nikolai
Bähr, Andrea
Blutke, Andreas
Landbrecht-Schessl, Christina
Wünsch, Annegret
Kessler, Barbara
Kurome, Mayuko
Hinrichs, Arne
Koopmans, Sietse-Jan
Krebs, Stefan
Kemter, Elisabeth
Rathkolb, Birgit
Nagashima, Hiroshi
Blum, Helmut
Ritzmann, Mathias
Wanke, Rüdiger
Aigner, Bernhard
Adamski, Jerzy
Hrabě de Angelis, Martin
Wolf, Eckhard
author_facet Renner, Simone
Martins, Ana Sofia
Streckel, Elisabeth
Braun-Reichhart, Christina
Backman, Mattias
Prehn, Cornelia
Klymiuk, Nikolai
Bähr, Andrea
Blutke, Andreas
Landbrecht-Schessl, Christina
Wünsch, Annegret
Kessler, Barbara
Kurome, Mayuko
Hinrichs, Arne
Koopmans, Sietse-Jan
Krebs, Stefan
Kemter, Elisabeth
Rathkolb, Birgit
Nagashima, Hiroshi
Blum, Helmut
Ritzmann, Mathias
Wanke, Rüdiger
Aigner, Bernhard
Adamski, Jerzy
Hrabě de Angelis, Martin
Wolf, Eckhard
author_sort Renner, Simone
collection PubMed
description Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INS(C93S) transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic β-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wild-type sows, piglets from hyperglycemic mothers showed impaired glucose tolerance and insulin resistance (homeostatic model assessment of insulin resistance: +3-fold in males; +4.4-fold in females) prior to colostrum uptake. Targeted metabolomics in the fasting and insulin-stimulated state revealed distinct alterations in the plasma metabolic profile of piglets from hyperglycemic mothers. They showed increased levels of acylcarnitines, gluconeogenic precursors such as alanine, phospholipids (in particular lyso-phosphatidylcholines) and α-aminoadipic acid, a potential biomarker for type 2 diabetes. These observations indicate that mild gestational hyperglycemia can cause impaired glucose tolerance, insulin resistance and associated metabolic alterations in neonatal offspring of a large-animal model born at a developmental maturation status comparable to human babies.
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spelling pubmed-67379532019-09-12 Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring Renner, Simone Martins, Ana Sofia Streckel, Elisabeth Braun-Reichhart, Christina Backman, Mattias Prehn, Cornelia Klymiuk, Nikolai Bähr, Andrea Blutke, Andreas Landbrecht-Schessl, Christina Wünsch, Annegret Kessler, Barbara Kurome, Mayuko Hinrichs, Arne Koopmans, Sietse-Jan Krebs, Stefan Kemter, Elisabeth Rathkolb, Birgit Nagashima, Hiroshi Blum, Helmut Ritzmann, Mathias Wanke, Rüdiger Aigner, Bernhard Adamski, Jerzy Hrabě de Angelis, Martin Wolf, Eckhard Dis Model Mech Research Article Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INS(C93S) transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic β-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wild-type sows, piglets from hyperglycemic mothers showed impaired glucose tolerance and insulin resistance (homeostatic model assessment of insulin resistance: +3-fold in males; +4.4-fold in females) prior to colostrum uptake. Targeted metabolomics in the fasting and insulin-stimulated state revealed distinct alterations in the plasma metabolic profile of piglets from hyperglycemic mothers. They showed increased levels of acylcarnitines, gluconeogenic precursors such as alanine, phospholipids (in particular lyso-phosphatidylcholines) and α-aminoadipic acid, a potential biomarker for type 2 diabetes. These observations indicate that mild gestational hyperglycemia can cause impaired glucose tolerance, insulin resistance and associated metabolic alterations in neonatal offspring of a large-animal model born at a developmental maturation status comparable to human babies. The Company of Biologists Ltd 2019-08-01 2019-08-12 /pmc/articles/PMC6737953/ /pubmed/31308048 http://dx.doi.org/10.1242/dmm.039156 Text en © 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Renner, Simone
Martins, Ana Sofia
Streckel, Elisabeth
Braun-Reichhart, Christina
Backman, Mattias
Prehn, Cornelia
Klymiuk, Nikolai
Bähr, Andrea
Blutke, Andreas
Landbrecht-Schessl, Christina
Wünsch, Annegret
Kessler, Barbara
Kurome, Mayuko
Hinrichs, Arne
Koopmans, Sietse-Jan
Krebs, Stefan
Kemter, Elisabeth
Rathkolb, Birgit
Nagashima, Hiroshi
Blum, Helmut
Ritzmann, Mathias
Wanke, Rüdiger
Aigner, Bernhard
Adamski, Jerzy
Hrabě de Angelis, Martin
Wolf, Eckhard
Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
title Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
title_full Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
title_fullStr Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
title_full_unstemmed Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
title_short Mild maternal hyperglycemia in INS(C93S) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
title_sort mild maternal hyperglycemia in ins(c93s) transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737953/
https://www.ncbi.nlm.nih.gov/pubmed/31308048
http://dx.doi.org/10.1242/dmm.039156
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