In:
Disease Models & Mechanisms, The Company of Biologists
Abstract:
Alongside with 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 if metabolic programming effects occur due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INSC93S transgenic pigs, a novel genetically-modified large animal model expressing the mutant insulin (INS) C93S in the pancreatic beta cells, resulting 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 (HOMA-IR: +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, such as increased levels of fatty acid mitochondrial transport (e.g. acylcarnitines), gluconeogenic precursors as alanine, phospholipids, in particular lyso-phosphatidylcholines, and alpha-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.
Type of Medium:
Online Resource
ISSN:
1754-8411
,
1754-8403
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2019
detail.hit.zdb_id:
2451104-3