title: Diabetic conditions modulate the adenosine monophosphate-activated protein kinase of podocytes.
abstract: BACKGROUND
  Adenosine monophosphate-activated protein kinases (AMPKs), as a sensor of cellular energy status, have been known to play an important role in the pathophysiology of diabetes and its complications. Because AMPKs are known to be expressed in podocytes, it is possible that podocyte AMPKs could be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPKs in the pathological changes in podocytes induced by high-glucose (HG) and advanced glycosylation end products (AGEs) in diabetic proteinuria.
  
  
  METHODS
  We prepared streptozotocin-induced diabetic renal tissues and cultured rat and mouse podocytes under diabetic conditions with AMPK-modulating agents. The changes in AMPKα were analyzed with confocal imaging and Western blotting under the following conditions: (1) normal glucose (5mM, =control); (2) HG (30mM); (3) AGE-added; or (4) HG plus AGE-added.
  
  
  RESULTS
  The density of glomerularphospho-AMPKα in experimental diabetic nephropathy decreased as a function of the diabetic duration. Diabetic conditions including HG and AGE changed the localization of phospho-AMPKα from peripheral cytoplasm to internal cytoplasm and peri- and intranuclear areas in podocytes. HG reduced the AMPKα (Thr172) phosphorylation of rat podocytes, and similarly, AGEs reduced the AMPKα (Thr172) phosphorylation of mouse podocytes. The distributional and quantitative changes in phospho-AMPKα caused by diabetic conditions were preventable using AMPK activators, metformin, and 5-aminoimidazole-4-carboxamide-1β-riboside.
  
  
  CONCLUSIONS
  We suggest that diabetic conditions induce the relocation and suppression of podocyte AMPKα, which would be a suggestive mechanism in diabetic podocyte injury.
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Tae-Sun
authors.initials: TS
authors.lastname: Ha
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Pediatrics, College of Medicine, Chungbuk National University, Cheongju, Korea.
authors.forename: Ja-Ae
authors.initials: JA
authors.lastname: Nam
authors.affiliation: Department of Food Science and Technology, College of Natural Resources, Yeungnam University, Gyeongsan, Korea.
authors.forename: Gi-Dong
authors.initials: GD
authors.lastname: Han
keywords: Adenosine monophosphate-activated  protein kinase; Advanced glycosylation end products; Diabetic nephropathy; Podocyte