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Hyperglycemia-Induced Cardiac Damage Is Alleviated by Heat-Inactivated Lactobacillus reuteri GMNL-263 via Activation of the IGF1R Survival Pathway

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Abstract

Diabetes-induced cardiomyocyte apoptosis is one of the major causes of mortality in patients with diabetes. Numerous studies have indicated the beneficial effects of Lactobacillus reuteri GMNL-263. However, the protective effect of Lactobacillus reuteri GMNL-263 in cardiac damage associated with diabetes remains poorly understood. In this study, we aimed to investigate the protective effect of Lactobacillus reuteri GMNL-263 on cardiomyocytes in diabetic rats. Five-week-old male Wistar rats were categorized into normal control group, diabetes group (55 mg/kgw STZ-induced diabetes via intraperitoneal injection), and diabetic animals treated with Lactobacillus reuteri GMNL-263 (109 CFU/rat/day, oral administration for 4 weeks). The results were presented that oral administration of a high dose of Lactobacillus reuteri GMNL-263 in diabetic rats activated IGF1R cell survival pathways to decrease the Fas-dependent and mitochondrial-dependent apoptotic pathways induced by hyperglycemia. We found that GMNL-263 significantly attenuated cell apoptosis via the IGF1R survival pathway in diabetic rats. The findings of this study suggest that GMNL-263 treatment maybe an effective therapeutic approach for the prevention of cardiac apoptosis in patients with diabetes.

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Abbreviations

CFU:

Colony-forming unit

DM:

Diabetes mellitus

GMNL-32:

Lactobacillus paracasei GMNL-32

GMNL-89:

Lactobacillus reuteri GMNL-89

GMNL-263:

Lactobacillus reuteri GMNL-263

PI3K:

Phosphatidylinositol-3 kinase

STZ:

Streptozotocin

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling assay

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Acknowledgments

This work is supported grant CMU-103-ASIA-13 from China Medical University and Asia University. We would like to acknowledge Dr. Hao-Chin Wang and Dr. B. Mahalakshmi, who provided suggestions during the writing of this manuscript draft.

Author information

Author notes

  1. Ker-Ping Koay and Wei-Wen Kuo share equal contribution.

Authors and Affiliations

  1. Department of Anesthesia, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Ker-Ping Koay & Hsiang-Ning Luk

  2. Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Bruce Chi-Kang Tsai & Chih-Yang Huang

  3. Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan

    Chia-Hua Kuo

  4. Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  5. Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan

    Wei-Wen Kuo

  6. Department of Nursing, MeiHo University, Pingtung, Taiwan

    Cecilia Hsuan Day

  7. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Ray-Jade Chen

  8. Department of Cardiology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Michael Yu-Chih Chen

  9. Department of Biotechnology, Bharathiar University, Coimbatore, India

    V. Vijaya Padma

  10. Department of Biological Science and Technology, Asia University, Taichung, Taiwan

    Chih-Yang Huang

  11. Center of General Education, Tzu Chi University of Science and Technology, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

    Chih-Yang Huang

  12. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

  13. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Chih-Yang Huang

Authors
  1. Ker-Ping Koay
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  2. Bruce Chi-Kang Tsai
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  3. Chia-Hua Kuo
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  5. Hsiang-Ning Luk
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  6. Cecilia Hsuan Day
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  7. Ray-Jade Chen
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  10. Chih-Yang Huang
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Contributions

Conceptualization: Ker-Ping Koay, Chia-Hua Kuo, and Chih-Yang Huang; data curation: Bruce Chi-Kang Tsai and Wei-Wen Kuo; formal analysis: Hsiang-Ning Luk, Bruce Chi-Kang Tsai, and Chih-Yang Huang; funding acquisition: Wei-Wen Kuo and Chih-Yang Huang; project administration: Cecilia Hsuan Day, Ray-Jade Chen, and Michael Yu-Chih Chen; resources: Ray-Jade Chen and Michael Yu-Chih Chen; supervision: Chih-Yang Huang; writing—original draft: Bruce Chi-Kang Tsai; writing—review and editing: Ker-Ping Koay, V. Vijaya Padma, Wei-Wen Kuo, and Chih-Yang Huang.

Corresponding author

Correspondence to Chih-Yang Huang.

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All animal experiment was approved by the Institute Animal Care and Use Committee of China Medical University, Taichung, Taiwan (2017-121).

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Koay, KP., Tsai, B.CK., Kuo, CH. et al. Hyperglycemia-Induced Cardiac Damage Is Alleviated by Heat-Inactivated Lactobacillus reuteri GMNL-263 via Activation of the IGF1R Survival Pathway. Probiotics & Antimicro. Prot. 13, 1044–1053 (2021). https://doi.org/10.1007/s12602-021-09745-z

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