title: Insulin signaling: implications for podocyte biology in diabetic kidney disease.
abstract: OBJECTIVE
  Several key elements of the insulin signaling cascade contribute to podocyte function and survival. While it was initially thought that the consequences of altered insulin signaling to podocyte function was strictly related to altered glucose uptake, it has become clear that upstream signaling events involved in cell survival, lipid metabolism or nutrient sensing and modulated by insulin are strong independent contributors to podocyte function.
  
  
  RESULTS
  Akt2, the major isoform of Akt activated following cellular insulin stimulation, protects against the progression of renal disease in nephron-deficient mice, and podocyte-specific deletion of Akt2 results in a more rapid progression of experimental glomerular disease. In diabetes, podocyte mammalian target of rapamycin activation clearly contributes to podocyte injury and regulated autophagy. Furthermore, podocyte-specific glucose transporter type 4 (GLUT4) deficiency protects podocytes by preventing mammalian target of rapamycin signaling independently of glucose uptake. Finally, intracellular lipids have been recently recognized as major modulators of podocyte insulin signaling and as a new therapeutic target.
  
  
  CONCLUSIONS
  The identification of new contributors to podocyte insulin signaling is of extreme translational value as it may lead to new drug development strategies for diabetic kidney disease, as well as for other proteinuric kidney diseases.
authors.affiliation: aChildren's Renal Unit, University of Bristol, Bristol Royal Hospital for Children, Bristol, UK bKatz Family Drug Discovery Center and Division of Nephrology and Hypertension, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Coward
authors.forename: Alessia
authors.initials: A
authors.lastname: Fornoni
mesh_terms: D000818:Animals; D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D051275:Glucose Transporter Type 4 / Q000172:deficiency; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050199:Podocytes / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases