title: Dietary glutamine supplementation enhances endothelial progenitor cell mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.
abstract: 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.
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shiau-Tsz
authors.initials: ST
authors.lastname: Su
authors.affiliation: Department of Nutrition and Health Sciences, Chinese Culture University, Taipei, Taiwan.
authors.forename: Chiu-Li
authors.initials: CL
authors.lastname: Yeh
authors.affiliation: Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hou
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Man-Hui
authors.initials: MH
authors.lastname: Pai
authors.affiliation: School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address: sangling@tmu.edu.tw.
authors.forename: Sung-Ling
authors.initials: SL
authors.lastname: Yeh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000178:diet therapy / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000178:diet therapy; D019587:Dietary Supplements; D066026:Endothelial Progenitor Cells / Q000187:drug effects*; D005973:Glutamine / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D007511:Ischemia / Q000178:diet therapy* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005973:Glutamine; D013311:Streptozocin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: CD31; Diabetic ischemic limb; Endothelial progenitor cells; Glutamine; Hypoxia-inducible factor-1