title: Effect of cartilage oligomeric matrix protein angiopoietin-1 on peripheral nerves in db/db diabetic mice.
abstract: BACKGROUND
  Vascular and inflammatory processes have been reported to be factors in the pathogenesis of diabetic neuropathy. Angiopoietin-1 (Ang1) plays essential roles in regulating vascular growth, development, maturation, permeability, and inflammation.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of cartilage oligomeric matrix protein (COMP)-Ang1, which is a soluble, stable, potent Ang1 variant, on peripheral nerves in db/db diabetic mice.
  
  
  METHODS
  The db/db diabetic mice were randomized into 2 groups based on their weight and glucose level and treated with recombinant adenovirus (Ade), expressing either COMP-Ang1 or the β-galactosidase gene (LacZ) (control), for 8 weeks. Immunohistochemistry was performed using a polyclonal antibody of antiprotein gene product and a secondary antibody. Intraepidermal nerve fiber density (IENFD) was quantified as nerve fiber abundance per unit length of epidermis (IENF/mm). In addition, the total capillary length (TCL) per unit length of epidermis was summed (mm/mm(2)). All slides were coded and the capillary length and the number of nerve fibers were calculated by a blinded observer.
  
  
  RESULTS
  Ten diabetic db/db mice (mean [SD] weight, 38.7 [1.95] g) were randomized to receive Ade-COMP-Ang1 or Ade-LacZ. IENFD was significantly greater in the Ade-COMP-Ang1 group compared with the Ade-LacZ group (mean [SD] 8.95 [3.30] vs 3.57 [0.73]/mm; P < 0.05). TCL was also significantly greater in the Ade-COMP-Ang1 group (2.79 [0.99] vs 2.04 [0.58] mm/mm(2); P < 0.05). Compared with baseline, fasting blood glucose concentration after 8 weeks of treatment decreased significantly more in the Ade-COMP-Ang1 group than in the Ade-LacZ group (489 [45] to 361 [81] vs 495 [48] to 521 [70] mg/dL; P < 0.05).
  
  
  CONCLUSIONS
  These results suggest that Ade-COMP-Ang1 might have had proliferative effects on peripheral nerve and cutaneous capillaries in this small animal study. Further investigation of the metabolic effect, target site, and related mediator of COMP-Ang1 is needed.
authors.affiliation: Endocrinology and Metabolism and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Heung Yong
authors.initials: HY
authors.lastname: Jin
authors.affiliation: Endocrinology and Metabolism and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Ming Han
authors.initials: MH
authors.lastname: Piao
authors.affiliation: Endocrinology and Metabolism and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Endocrinology and Metabolism and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Hong Sun
authors.initials: HS
authors.lastname: Baek
authors.affiliation: Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.affiliation: Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.affiliation: Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.affiliation: Bucheon Sejong Hospital, Bucheon, South Korea.
authors.forename: Chong Hwa
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Biomedical Research Center and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.affiliation: Endocrinology and Metabolism and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Park
keywords: COMP-angiopoietin-1; db/db diabetic mice; peripheral neuropathy