Journal of Molecular Medicine

, Volume 96, Issue 5, pp 373–381 | Cite as

Preservation of renal function in chronic diabetes by enhancing glomerular glucose metabolism

  • Weier Qi
  • Qian Li
  • Daniel Gordin
  • George L. King


Diabetic nephropathy (DN) affects approximately 30–40% of patients with type 1 (T1DM) and type 2 diabetes (T2DM). It is a major cause of end-stage renal disease (ESRD) for the developed world. Hyperglycemia and genetics are major causal factors for the initiation and progression of DN. Multiple abnormalities in glucose and mitochondrial metabolism induced by diabetes likely contribute to the severity of DN. Recent clinical studies in people with extreme duration of T1DM (> 50 years, Joslin Medalist Study) have supported the importance of endogenous protective factors to neutralize the toxic effects of hyperglycemia on renal and other vascular tissues. Using renal glomeruli from these patients (namely Medalists) with and without DN, we have shown the importance of increased glycolytic flux in decreasing the accumulation of glucose toxic metabolites, improving mitochondrial function, survival of glomerular podocytes, and reducing glomerular pathology. Activation of a key glycolytic enzyme, pyruvate kinase M2 (PKM2), resulted in the normalization of renal hemodynamics and mitochondrial and glomerular dysfunction, leading to the mitigation of glomerular pathologies in several mouse models of DN.


Diabetic nephropathy Glucose metabolism Glycolysis PKM2 Metabolites 


Funding information

W.Q. was supported by JDRF Fellowship. G.L.K. was funded by NIH 1DP3DK112192-01, NIH P30DK036836, JDRF 8-2005-358, JDRF 18-2008-363, and JDRF 17-2011-47. This work was supported in part by Mary K. Iacocca Fellowship provided by the Iacocca Foundation (D.G.). D.G. was also supported by grants from the Medical Society of Finland (Finska Läkaresällskapet), the Wilhelm and Else Stockmann Foundation, the Biomedicum Helsinki Foundation, the Finnish Medical Foundation, the Swedish Cultural Foundation in Finland, and the Dorothea Olivia, Karl Walter och Jarl Walter Perkléns Foundation.

Supplementary material

109_2018_1630_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Weier Qi
    • 1
    • 2
  • Qian Li
    • 1
  • Daniel Gordin
    • 1
  • George L. King
    • 1
  1. 1.Research Division, Joslin Diabetes CenterHarvard Medical SchoolBostonUSA
  2. 2.Translational Research and Early Clinical Development, Cardiovascular and Metabolic ResearchAstraZenecaMölndalSweden

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