Diabetes is a metabolic disorder with increased risk of
vascular diseases. Tissue
ischemia may occur with
diabetic vascular complications. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. This study investigated the effects of oral
glutamine (GLN) supplementation on circulating
EPC mobilization and expression of tissue
EPC-releasing markers in diabetic mice subjected to limb
ischemia. Diabetes was induced by a daily
intraperitoneal injection of
streptozotocin for 5 days. Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One of the nonischemic and 3 ischemic groups were fed the control diet, while the remaining 4 groups received diets with identical components except that part of the
casein was replaced by GLN. The respective diets were fed to the mice for 3 weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb
ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or 21 days after
ischemia. Their blood and ischemic muscle tissues were collected for further analyses. Results showed that plasma matrix
metallopeptidase (MMP)-9 and the circulating
EPC percentage increased after limb
ischemia in a diabetic condition. Compared to groups without GLN, GLN supplementation up-regulated plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1,
hypoxia-inducible factor-1 and
vascular endothelial growth factor gene expression. The CD31-immunoreactive intensities were also higher in the ischemic limb. These findings suggest that GLN supplementation enhanced circulating
EPC mobilization that may promote endothelium repair at ischemic tissue in diabetic mice subjected to limb
ischemia.