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Renner, S.* ; Martins, A.S.* ; Streckel, E.* ; Braun-Reichhart, C.* ; Backman, M.* ; Prehn, C. ; Klymiuk, N.* ; Bähr, A.* ; Blutke, A. ; Landbrecht-Schessl, C.* ; Wünsch, A.* ; Kessler, B.* ; Kurome, M.* ; Hinrichs, A.* ; Koopmans, S.J.* ; Krebs, S.* ; Kemter, E.* ; Rathkolb, B. ; Nagashima, H.* ; Blum, H.* ; Ritzmann, M.* ; Wanke, R.* ; Aigner, B.* ; Adamski, J. ; Hrabě de Angelis, M. ; Wolf, E.*

Mild maternal hyperglycemia in INSC93S transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring.

Dis. Model. Mech. 12:dmm039156 (2019)
Publ. Version/Full Text Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 INSC93S transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic beta-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wildtype 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 lysophosphatidylcholines) and a-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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Maternal Diabetes ; Pig ; Transgenic ; Developmental Programming ; Metabolomics; Insulin-resistance; Fetal; Associations; Mutations; Markers; Obesity; Models; Growth; Mutant
ISSN (print) / ISBN 1754-8403
e-ISSN 1754-8411
Journal Disease Models and Mechanisms
Quellenangaben Volume: 12, Issue: 8, Pages: , Article Number: dmm039156 Supplement: ,
Publisher Company of Biologists
Publishing Place Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Experimental Genetics (IEG)
Research Unit Analytical Pathology (AAP)