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Over-expression of muscle glycogen synthase in human diabetic nephropathy

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Abstract

Diabetic nephropathy (DN) is a major complication of diabetic patients and the leading cause of end-stage renal disease. Glomerular dysfunction plays a critical role in DN, but deterioration of renal function also correlates with tubular alterations. Human DN is characterized by glycogen accumulation in tubules. Although this pathological feature has long been recognized, little information exists about the triggering mechanism. In this study, we detected over-expression of muscle glycogen synthase (MGS) in diabetic human kidney. This enhanced expression suggests the participation of MGS in renal metabolic changes associated with diabetes. HK2 human renal cell line exhibited an intrinsic ability to synthesize glycogen, which was enhanced after over-expression of protein targeting to glycogen. A correlation between increased glycogen amount and cell death was observed. Based on a previous transcriptome study on human diabetic kidney disease, significant differences in the expression of genes involved in glycogen metabolism were analyzed. We propose that glucose, but not insulin, is the main modulator of MGS activity in HK2 cells, suggesting that blood glucose control is the best approach to modulate renal glycogen-induced damage during long-term diabetes.

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Acknowledgments

The authors thank Dr. Ilona Concha and Elizabeth Mann for correcting the English manuscript. Microscopy analysis was performed at Centro de Microscopía Avanzada (CMA)-Bio Bio, Universidad de Concepción, Concepción, Chile. This study was supported by grants from Fondo Nacional de Desarrollo Científico y Tecnológico from Chilean State: FONDECYT 1131033 to A. Yañez; FONDECYT 3120144 to R. Bertinat.

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The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Facultad de Medicina, Universidad San Sebastián, Puerto Montt, Chile

    Rodrigo Gatica

  2. Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Isla Teja S/N, Valdivia, Chile

    Romina Bertinat, Pamela Silva, Pamela Kairath, Juan C. Slebe & Alejandro J. Yáñez

  3. Institute for Research in Biomedicine (IRB), University of Barcelona, Barcelona, Spain

    Felipe Slebe

  4. Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Fabián Pardo

  5. Department of Nephrology and Renal Transplantation, Hospital Clinic, Barcelona, Spain

    María J. Ramírez & José M. Campistol

  6. Centro de Microscopía Avanzada, CMA-Bío Bío, Universidad de Concepción, Concepción, Chile

    Francisco Nualart & Alejandro J. Yáñez

  7. Universidad de Barcelona, Barcelona, Spain

    Carme Caelles

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  1. Rodrigo Gatica
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Correspondence to Alejandro J. Yáñez.

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Rodrigo Gatica and Romina Bertinat have contributed equally to this work.

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Gatica, R., Bertinat, R., Silva, P. et al. Over-expression of muscle glycogen synthase in human diabetic nephropathy. Histochem Cell Biol 143, 313–324 (2015). https://doi.org/10.1007/s00418-014-1290-2

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