title: Diabetes exacerbates inflammatory responses to ischemia-reperfusion.
abstract: BACKGROUND
  Diabetes is associated with an increased incidence of ischemic organ damage. The objectives of present study were to compare the leukocyte-endothelial cell adhesive interactions and albumin leakage response of mesenteric venules to ischemia-reperfusion between control rats, rats with streptozotocin-induced diabetes, and rats with hyperglycemia induced by glucose infusion and to define the molecular determinants of the leukocyte accumulation elicited by ischemia-reperfusion in diabetic rats.
  
  
  RESULTS
  Under baseline conditions, lower venular shear rates and an increased number of rolling leukocytes were noted in diabetic rats, whereas the number of adherent and emigrated leukocytes did not differ from that in control rats. Spontaneous albumin leakage from mesenteric venules was markedly increased in diabetic rats but not in hyperglycemic nondiabetic rats. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration and albumin leakage in diabetic rats. Acute elevation of glucose levels did not modify the microvascular responses to ischemia-reperfusion compared with control rats. Antibodies directed against CD11/CD18, intercellular adhesion molecule-1 (ICAM-1), or P-selectin but not L-selectin significantly decreased the number of adherent and emigrated leukocytes after ischemia-reperfusion in diabetic rats. However, none of the antibodies significantly attenuated the increased albumin leakage response to ischemia-reperfusion in diabetic rats.
  
  
  CONCLUSIONS
  These results indicate that diabetes mellitus is associated with exaggerated leukocyte-endothelial cell adhesion and albumin leakage responses to ischemia-reperfusion. The enhanced leukocyte accumulation in response to ischemia-reperfusion is mediated by CD11/CD18-ICAM-1 interactions (firm adhesion) and P-selectin (rolling). The exaggerated albumin leakage response to ischemia-reperfusion in diabetics is not mediated by the recruited inflammatory cells.
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
authors.forename: J
authors.initials: J
authors.lastname: Panés
authors.forename: I
authors.initials: I
authors.lastname: Kurose
authors.forename: D
authors.initials: D
authors.lastname: Rodriguez-Vaca
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: P
authors.initials: P
authors.lastname: Tso
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D016827:CD8 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000473:pathology; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology*
chemical_list: D000418:Albumins; D016827:CD8 Antigens; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1