Kidney growth, hypertrophy and the unifying mechanism of diabetic complications.
Michael Brownlee has proposed a 'Unifying Mechanism' of hyperglycemia-induced damage in diabetes mellitus. At the crux of this hypothesis is the generation of reactive oxygen species (ROS), and their impact on glycolytic pathways. Diabetes is the leading cause of chronic kidney failure. In the early phase of diabetes, prior to establishment of proteinuria or fibrosis, comes kidney growth and hyperfiltration. This early growth phase consists of an early period of hyperplasia followed by hypertrophy. Hypertrophy also contributes to cellular oxidative stress, and may precede the ROS perturbation of glycolytic pathways described in the Brownlee proposal. This increase in growth promotes hyperfiltration, and along with the hypertrophic phenotype appears required for hyperglycemia-induced cell damage and the progression of downstream diabetic complications. Here we will evaluate this growth phenomenon in the context of diabetes mellitus.
Satriano
J
J
Division of Nephrology-Hypertension, Department of Medicine, The Veterans Administration San Diego Healthcare System, University of California San Diego, San Diego, CA 92161, USA. jsatriano@ucsd.edu
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology; D048909:Diabetes Complications / Q000209:etiology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology*; D000518:Eflornithine / Q000494:pharmacology; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology; D039642:Eukaryotic Initiation Factors; D025461:Feedback, Physiological; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006984:Hypertrophy; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology*; D007684:Kidney Tubules / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D053858:Metabolic Networks and Pathways / Q000502:physiology; D009955:Ornithine Decarboxylase / Q000502:physiology; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009955:Ornithine Decarboxylase; D000518:Eflornithine