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Effects of dietary glutamine supplementation on immune cell polarization and muscle regeneration in diabetic mice with limb ischemia

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Abstract

Purpose

Diabetes is a chronic inflammatory disorder resulting in endothelial dysfunction which contributes to peripheral arterial disease and limb ischemia. Leukocytes play critical roles in vascular and tissue remodelling after ischemia. This study investigated the effects of dietary glutamine (GLN) supplementation on immune cell polarization in diabetic mice subjected to limb ischemia.

Methods

Diabetes was induced by an intraperitoneal injection of streptozotocin for 5 consecutive days in C57BL/6J mice. Diabetic mice were fed the AIN-93 diet or an AIN-93 diet in which a part of the casein was replaced by GLN. After 3 weeks of the dietary intervention, mice were subjected to unilateral femoral artery ligation to induce limb ischemia.

Results

GLN supplementation enhanced the proportion of anti-inflammatory monocytes and regulatory T cells in the blood. Expression of C-C motif chemokine receptor 5 by activated CD4+ T cells was promoted and prolonged in the GLN-supplemented group. GLN downregulated the percentage of M1 macrophages in muscle tissues which was correlated with lower levels of C-C motif chemokine ligand 2 in plasma. The muscle M1/M2 ratio was also reduced in the GLN group. Gene expression of interleukin-6 was suppressed by GLN supplementation, while expression levels of the peroxisome proliferator-activated receptor γ and myogenic differentiation 1 genes were elevated in post-ischemic muscles. Histological findings also indicated that muscle regeneration was accelerated in the GLN group.

Conclusions

GLN supplementation in diabetic mice may exert more-balanced polarization of CD4+ T cells, monocytes, and macrophages, thus attenuating inflammatory responses and contributing to muscle regeneration after limb ischemia.

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Acknowledgements

This study was supported by research grants (MOST 103-2320-B-038-016-MY3 and MOST 106-2314-B-038-086) from the Ministry of Science and Technology, Taipei, Taiwan.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Man-Hui Pai

  2. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan

    Cing-Syuan Lei, Shiau-Tsz Su & Sung-Ling Yeh

  3. Master Program in Food Safety, College of Nutrition, Taipei Medical University, 250 Wu-Hsing Street, Taipei, 11031, Taiwan

    Yu-Chen Hou

  4. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan

    Yu-Chen Hou

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  1. Man-Hui Pai
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  2. Cing-Syuan Lei
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Correspondence to Yu-Chen Hou.

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Pai, MH., Lei, CS., Su, ST. et al. Effects of dietary glutamine supplementation on immune cell polarization and muscle regeneration in diabetic mice with limb ischemia. Eur J Nutr 59, 921–933 (2020). https://doi.org/10.1007/s00394-019-01951-4

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  • DOI: https://doi.org/10.1007/s00394-019-01951-4

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