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

Man Hui Pai, Cing Syuan Lei, Shiau Tsz Su, Sung Ling Yeh, Yu Chen Hou

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)921-933
Number of pages13
JournalEuropean Journal of Nutrition
Issue number3
Publication statusPublished - Apr 1 2020


  • Diabetic ischemic limb
  • Glutamine
  • Immune cell polarization
  • Muscle regeneration

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


Dive into the research topics of 'Effects of dietary glutamine supplementation on immune cell polarization and muscle regeneration in diabetic mice with limb ischemia'. Together they form a unique fingerprint.

Cite this