The role of metabolic and haemodynamic factors in podocyte injury in diabetes

Diabetes Metab Res Rev. 2011 Mar;27(3):207-15. doi: 10.1002/dmrr.1164.

Abstract

Podocyte loss is a common feature in human diabetes as well as in experimental diabetes in rodents. Almost all components of the diabetic milieu lead to serious podocyte stress, driving the cells towards cell cycle arrest and hypertrophy, detachment and apoptosis. Common pathway components induced by high glucose and advanced glycation end-products are reactive oxygen species, cyclin-dependent kinases (p27(Kip1)) and transforming growth factor-beta. In addition, mechanical stresses by stretch or shear forces, insulin deficiency or insulin resistance are independent components resulting in podocyte apoptosis and detachment. In this review, we discuss the common pathways leading to podocyte death as well as novel pathways and concepts of podocyte dedifferentiation and detachment that influence the progression of diabetic glomerulopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actins / physiology
  • Apoptosis
  • Chemokines / physiology
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Cytokines / physiology
  • Diabetes Mellitus, Type 1 / pathology*
  • Diabetes Mellitus, Type 2 / pathology*
  • Diabetic Nephropathies / physiopathology
  • Glucose / metabolism
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Hyperglycemia / physiopathology
  • Insulin / physiology
  • Insulin Resistance
  • Podocytes / metabolism
  • Podocytes / pathology*
  • Stress, Mechanical
  • Transforming Growth Factor beta / metabolism

Substances

  • Actins
  • Chemokines
  • Cytokines
  • Glycation End Products, Advanced
  • Insulin
  • Transforming Growth Factor beta
  • Cyclin-Dependent Kinase Inhibitor p27
  • Glucose