title: Altered gap junctional communication and renal haemodynamics in Zucker fatty rat model of type 2 diabetes.
abstract: OBJECTIVE
  We examined the link between altered gap junctional communication and renal haemodynamic abnormalities in diabetes in studies performed on Zucker lean (ZL) and the Zucker diabetic fatty (ZDF) rat model of type 2 diabetes.
  
  
  METHODS
  The abundance of connexin (Cx) 37, 40 and 43 was assessed by western blot and immunohistochemistry. Renal haemodynamics was characterised with GAP peptides, which are Cx mimetics, to inhibit gap junctions as a probe in both strains.
  
  
  RESULTS
  ZDF rats exhibited higher plasma glucose, 8-epi-prostaglandin F2α excretion, renal plasma flow and GFR than ZL rats. In ZDF rat kidney phosphorylation of Cx43 was enhanced compared with that in ZL rats. Immunohistochemical study revealed that the density of abundance of Cx37 in renin-secreting cells was significantly reduced in ZDF rats. Although renal autoregulation was markedly impaired in ZDF rats, it was preserved in ZL rats. GAP27 for Cx37,43 and for Cx40 impaired renal autoregulation in ZL rats, but failed to induce further alterations in renal autoregulation in ZDF rats.
  
  
  CONCLUSIONS
  Our findings indicate that ZDF rats have glomerular hyperfiltration with impaired autoregulation. They also demonstrate enhanced phosphorylation of Cxs and reduced production of Cxs in ZDF rat kidney, especially of Cx37 in renin-secreting cells. Finally, our data suggest that an impairment of gap junctional communication in juxtaglomerular apparatus plays a role in altered renal autoregulation in diabetes.
authors.affiliation: Department of Nephrology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo Moroyama, Iruma, Saitama 350-0495, Japan. takenaka@saitama-med.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: D J
authors.initials: DJ
authors.lastname: Chaston
authors.forename: C E
authors.initials: CE
authors.lastname: Hill
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D007150:Immunohistochemistry; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D011924:Rats, Zucker; D012084:Renin-Angiotensin System / Q000502:physiology; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein