Protein Kinase C in Diabetic Renal Involvement, the Perspective of its Inhibition

  • Daisuke Koya
  • George L. King


The Diabetes Control and Complication Trial recently reported that the strict maintenance of euglycemia by intensive insulin treatment can prevent the development and progression of diabetic nephropathy [1], suggesting the adverse effects of hyperglycemia on metabolic pathways are main cause of chronic complications in diabetes such as kidney disease. The importance of hyperglycemia in the development of diabetic nephropathy is supported by the results of Heilig et al. who have found that the overexpression of glucose transporter 1 (GLUTI) into glomerular mesangial cells enhanced the production of extracellular matrix components which can contribute mesangial expansion and finally glomerulosclerosis, even in normal glucose levels [2]. Multiple biochemical mechanisms have been proposed to explain the adverse effects of hyperglycemia. Activation of diacylglycerol (DAG) -protein kinase C (PKC) pathway [3,4], enhanced polyol pathway related with myo-inositol depletion [5], altered redox state [6], overproduction of advanced glycation products [7], and enhanced growth factor and cytokine production [8.9] have all been proposed as potential cellular mechanisms by which hyperglycemia induces the chronic diabetic complications.


Diabetic Nephropathy Arachidonic Acid Release Urinary Albumin Excretion Rate Glomerular Mesangial Cell Mesangial Expansion 
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Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • Daisuke Koya
    • 1
  • George L. King
    • 2
    • 3
  1. 1.Third Department of MedicineShiga University of Medical ScienceSeta, Otsu Shiga 520-21Japan
  2. 2.Research Division, Joslin Diabetes CenterDepartment of MedicineBrighamUSA
  3. 3.Women’s Hospital and Harvard Medical SchoolBostonUSA

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