Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats

Erin E Gordon; Benjamin E Reinking; Shanming Hu; Jianrong Yao; Kok L Kua; Areej K Younes; Chunlin Wang; Jeffrey L Segar; Andrew W Norris

doi:10.1155/2015/479565

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Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats

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Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats

Erin E Gordon, Benjamin E Reinking, Shanming Hu, Jianrong Yao, Kok L Kua, Areej K Younes, Chunlin Wang, Jeffrey L Segar and Andrew W Norris

Journal of diabetes research, Vol.2015, pp.479565-11

2015

DOI: 10.1155/2015/479565

PMCID: PMC4439465

PMID: 26064981

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Abstract

Cardiac septal overgrowth complicates 10–40% of births from diabetic mothers, but perplexingly hyperglycemia markers during pregnancy are not reliably predictive. We thus tested whether fetal exposure to hyperglycemia is sufficient to induce fetal cardiac septal overgrowth even in the absence of systemic maternal diabetes. To isolate the effects of hyperglycemia, we infused glucose into the blood supply of the left but not right uterine horn in nondiabetic pregnant rats starting on gestational day 19. After 24 h infusion, right-sided fetuses and dams remained euglycemic while left-sided fetuses were moderately hyperglycemic. Echocardiograms in utero demonstrated a thickened cardiac septum among left-sided (glucose-exposed, 0.592 ± 0.016 mm) compared to right-sided (control, 0.482 ± 0.016 mm) fetuses. Myocardial proliferation was increased 1.5 ± 0.2-fold among left-sided compared to right-sided fetuses. Transcriptional markers of glucose-derived anabolism were not different between sides. However, left-sided fetuses exhibited higher serum insulin and greater JNK phosphorylation compared to controls. These results show that hyperglycemic exposure is sufficient to rapidly induce septal overgrowth even in the absence of the myriad other factors of maternal diabetes. This suggests that even transient spikes in glucose may incite cardiac overgrowth, perhaps explaining the poor clinical correlation of septal hypertrophy with chronic hyperglycemia.

Details

Title: Subtitle: Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats
Creators: Erin E Gordon - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Benjamin E Reinking - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Shanming Hu - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Jianrong Yao - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Kok L Kua - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Areej K Younes - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Chunlin Wang - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Jeffrey L Segar - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Andrew W Norris - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Journal of diabetes research, Vol.2015, pp.479565-11
DOI: 10.1155/2015/479565
PMID: 26064981
PMCID: PMC4439465
NLM abbreviation: J Diabetes Res
ISSN: 2314-6745
eISSN: 2314-6753
Publisher: Hindawi Publishing Corporation
Grant note: DOI: 10.13039/100002069, name: Fraternal Order of Eagles, award: R24 DK96518, R01 DK097820
Language: English
Date published: 2015
Academic Unit: Endocrinology and Diabetes; Cardiology; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology
Record Identifier: 9984025291002771

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