title: Microvascular alterations in diabetic mice correlate with level of hyperglycemia.
abstract: Vascular alterations are the most common causes of morbidity and mortality in diabetic patients. Despite the impact of endothelial dysfunction on microcirculatory properties, little is known about the endothelial cell alteration during the development of diabetes and its correlation to the metabolic situation. For that reason we continuously monitored in vivo functional and morphological alterations of the microvasculature in hyperglycemic and hyperinsulinemic transgenic UCP1/DTA mice with brown fat deficiency, using a dorsal skin-fold chamber preparation and fluorescence microscopy. UCP1/DTA mice showed a dramatic decrease in vascular density due to a remarkable reduction of small vessels. Vascular permeability and leukocyte endothelial interactions (LEIs) significantly increased. The extent of vascular alteration correlated with the extent of metabolic dysfunction. Decreased tissue perfusion observed in UCP1/DTA mice might play a role in impaired wound healing observed in diabetes. The increased permeability in subcutaneous tissue may serve as predictor of vascular changes in early stages of diabetes. The increased LEI and serum tumor necrosis factor-alpha levels, which mirror the inflammatory process, support the growing evidence of the inflammatory component of diabetic disease. The results suggest that anti-inflammatory strategies might be able to prevent vascular deterioration in early stages of diabetes. Further investigations are required to evaluate the benefit of such therapeutic strategies.
authors.affiliation: Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Algenstaedt
authors.forename: Christian
authors.initials: C
authors.lastname: Schaefer
authors.forename: Tanja
authors.initials: T
authors.lastname: Biermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hamann
authors.forename: Britta
authors.initials: B
authors.lastname: Schwarzloh
authors.forename: Heiner
authors.initials: H
authors.lastname: Greten
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rüther
authors.forename: Nils
authors.initials: N
authors.lastname: Hansen-Algenstaedt
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D001831:Body Temperature; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood / Q000473:pathology*; D004167:Diphtheria Toxin / Q000235:genetics; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000097:blood / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000473:pathology*; D008853:Microscopy; D010446:Peptide Fragments / Q000235:genetics; D012307:Risk Factors; D012867:Skin / Q000098:blood supply*
chemical_list: D001786:Blood Glucose; D004167:Diphtheria Toxin; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A