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

  • Annarita Gabriele
  • Daisuke Koya
  • George L. King


The Diabetes Control and Complications Trial (DCCT) and, more recently, the United Kingdom Prospective Diabetes Study (UKPDS) reported that the strict maintenance of euglycemia by intensive insulin treatment can delay the onset and slow the progression of diabetic nephropathy, respectively, in patients with type 1 and type 2 diabetes mellitus [1,2], suggesting that the adverse effects of hyperglycemia on metabolic pathways are main cause of long-term complications in diabetes such as kidney disease. The importance of hyperglycemia in the development of diabetic nephropathy is supported by the results of Heilig {ntet al. who have found that the overexpression of glucose transporter 1 (GLUT1) into glomerular mesangial cells enhanced the production of extracellular matrix components which can contribute mesangial expansion and finally glomerulosclerosis, even in normal glucose levels [3]. Multiple biochemical mechanisms have been proposed to explain the adverse effects of hyperglycemia. Activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway [4,5], enhanced polyol pathway related with myo-inositol depletion [6], altered redox state [7], overproduction of advanced glycation end products [8], and enhanced growth factor and cytokine production [9,10] have all been proposed as potential cellular mechanisms by which hyperglycemia induces the chronic diabetic complications.


Diabetic Nephropathy Connective Tissue Growth Factor United Kingdom Prospective Diabetes Study Arachidonic Acid Release Urinary Albumin Excretion Rate 
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Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Annarita Gabriele
    • 2
  • Daisuke Koya
    • 1
  • George L. King
    • 3
  1. 1.Third Department of MedicineShiga University of Medical ScienceSeta, Otsu ShigaJapan
  2. 2.Endocrinology Division, Department of Clinical ScienceLa Sapienza UniversityRomeItaly
  3. 3.Research Division, Joslin Diabetes Center, Department of MedicineHarvard Medical SchoolBostonUSA

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