title: Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in early streptozotocin-induced type 2 diabetic rats.
abstract: OBJECTIVE
  To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)-nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats.
  
  
  METHODS
  Wistar rats were randomly divided into normal control group, diabetic nephropathy (DN) group induced by high-fat feeding and streptozotocin, diabetic rats injected with adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD-IRES-EGFP as control. Blood and urine samples were collected. Endothelium-dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were measured by the Griess reaction and Western blot testing, respectively.
  
  
  RESULTS
  Injections of AD-AdipoQ significantly increased serum adiponectin levels and reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and malondialdehyde were significantly reduced in diabetic rats after injections of AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in diabetic rats, indicating increased proliferation of glomerular endothelial cells. However, AD-AdipoQ improved the increased proliferation of endothelial cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and reduced NO levels. This uncoupling of the VEGF-NO axis was partially improved by AD-AdipoQ.
  
  
  CONCLUSIONS
  Adiponectin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular VEGF-NO axis in early diabetic nephropathy.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Weifang, 261031, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Hou
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zhao
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism*; D004727:Endothelium / Q000187:drug effects; D005029:Ethylenediamines; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013424:Sulfanilamides; D016482:Urinalysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D005029:Ethylenediamines; C095000:Griess reagent; D013424:Sulfanilamides; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D013311:Streptozocin