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Intrauterine hyperglycemia-induced inflammatory signalling via the receptor for advanced glycation end products in the cardiac muscle of the infants of diabetic mother rats

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Abstract

Purpose

Gestational diabetes is associated with increased risk to the health of the mother and her offspring. In particular, the infants of diabetic mothers (IDMs) exhibit elevated levels of preterm birth, macrosomia, hypoglycemia, hypocalcemia, and cardiomyopathy. We have previously reported that IDMs showed abnormalities in cardiac Akt-related insulin signalling, and that these deficiencies in Akt-related signalling were attenuated by supplementing the maternal diet with fish-oil. Herein, we investigated whether the eicosapentaenoic acid (EPA) found in fish oil can be used to attenuate diabetes associated impairments in cardiomyocyte signalling.

Methods

Pregnant diabetic rats were administered streptozotocin before receiving EPA or water, and their infants were designated IDM/EPA, IDM/W. We assessed the potential molecular pathway for this effect in the primary cardiac cell from newborn rat hearts.

Results

Insulin resistance as determined by diminished GLUT4 translocation following insulin stimulation, the levels of advanced glycation end products (AGEs) and reactive oxygen species were elevated in the neonatal hearts of IDM/W compared with that seen in the offspring born from non-diabetic control animals. Similarly, the receptor of AGEs (RAGE) mRNA levels, reactive oxygen species and the amount of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) mRNA were higher in the hearts from the IDM/W when compared to that observed in the hearts of offspring born to non-diabetic animals. These deleterious effects of gestational diabetes were significantly decreased in the offspring of diabetic mothers receiving EPA supplementation.

Conclusions

Taken together, our data suggest that the EPA in fish oil may improve the impaired signalling and the excessive protein glycation in the cardiac muscles of infants exposed to intrauterine hyperglycemia.

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Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a grant from the Smoking Research Foundation and The Cardiovascular Research Fund, Tokyo, Japan.

Author information

Authors and Affiliations

  1. Department of Health and Nutrition, Takasaki University of Health and Welfare, 37-1 Nakaorui-machi, Takasaki, Gunma, 370-0033, Japan

    Ritsuko Kawaharada

  2. Department of Nutrition, Gunma Prefectural Cancer Center, 617-1, Takabayashinishi-machi, Ota, Gunma, 373-8550, Japan

    Haruna Masuda

  3. Department of Applied Chemistry, Faculty of Agriculture, Tokyo University Graduate School of Agricultural and Life Sciences, 1-1-1, Yayoi, Bunkyo, Tokyo, 113-8657, Japan

    Zhenyi Chen

  4. Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA

    Eric Blough

  5. Department of Pharmacology, Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA

    Eric Blough

  6. Department of Pharmacology, Physiology and Toxicology, Marshall University, Huntington, WV, USA

    Eric Blough

  7. Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Eric Blough

  8. Maki Hospital, 71-1, Tsukunawa-machi, Takasaki, Gunma, 370-0075, Japan

    Tomoko Kohama

  9. Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi, Gunma, 371-8511, Japan

    Akio Nakamura

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  1. Ritsuko Kawaharada
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Correspondence to Akio Nakamura.

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All experimental protocols were conducted in accordance with the Institutional Regulations for Animal Experiments and Fundamental Guidelines for Proper Conduct of Animal Experiments and Related Activities in Academic Research Institutions under the Jurisdiction of the Japanese Ministry of Education, Culture, Sports, Science and Technology.

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Kawaharada, R., Masuda, H., Chen, Z. et al. Intrauterine hyperglycemia-induced inflammatory signalling via the receptor for advanced glycation end products in the cardiac muscle of the infants of diabetic mother rats. Eur J Nutr 57, 2701–2712 (2018). https://doi.org/10.1007/s00394-017-1536-6

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  • DOI: https://doi.org/10.1007/s00394-017-1536-6

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