Carnosine treatment largely prevents alterations of renal carnosine metabolism in diabetic mice (original) (raw)

Abstract

Recently, we identified an allelic variant of human carnosinase 1 (CN1) that results in increased enzyme activity and is associated with susceptibility for diabetic nephropathy in humans. Investigations in diabetic (db/db) mice showed that carnosine ameliorates glucose metabolism effectively. We now investigated the renal carnosinase metabolism in db/db mice. Kidney CN1 activity increased with age and was significantly higher in diabetic mice compared to controls. Increased CN1 activity did not affect renal carnosine levels, but anserine concentrations were tenfold lower in db/db mice compared to controls (0.24 ± 0.2 vs. 2.28 ± 0.3 nmol/mg protein in controls; p < 0.001). Homocarnosine concentrations in kidney tissue were low in both control and db/db mice (below 0.1 nmol/mg protein, p = n.s.). Carnosine treatment for 4 weeks substantially decreased renal CN1 activity in diabetic mice (0.32 ± 0.3 in non-treated db/db vs. 0.05 ± 0.05 μmol/mg/h in treated db/db mice; p < 0.01) close to normal activities. Renal anserine concentrations increased significantly (0.24 ± 0.2 in non-treated db/db vs. 5.7 ± 1.2 μmol/mg/h in treated db/db mice; p < 0.01), while carnosine concentrations remained unaltered (53 ± 6.4 in non-treated vs. 61 ± 15 nmol/mg protein in treated db/db mice; p = n.s.). Further, carnosine treatment halved proteinuria and reduced vascular permeability to one-fifth in db/db mice. In renal tissue of diabetic mice carnosinase activity is significantly increased and anserine concentrations are significantly reduced compared to controls. Carnosine treatment largely prevents the alterations of renal carnosine metabolism.

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Acknowledgments

We thank Kristina Klingbeil for technical assistance. Part of this study was supported by the EU-funded specific-target project PREDICTIONS on the identification of risk factors for the development of diabetic nephropathy as well as grants by the Deutsche Forschungsgemeinschaft to M. Mack and J Zschocke (Ma2510/3-1 and Zs17/5-1). Family Erling Persson Foundation, The European Commission project FUNCFOOD (FP7-KBBE-2009-245030), Novo Nordic Foundation and Swedish Research Council.

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Authors and Affiliations

1. Division of Metabolic Diseases, Centre for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120, Heidelberg, Germany
   Verena Peters
2. Division of Pediatric Nephrology, Centre for Pediatric and Adolescent Medicine, Heidelberg, Germany
   Claus P. Schmitt
3. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria
   Johannes Zschocke
4. Department of Internal Medicine, Institute of Pathology, Heidelberg, Germany
   Marie-Luise Gross
5. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
   Kerstin Brismar & Elisabete Forsberg

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1. Verena Peters
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2. Claus P. Schmitt
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3. Johannes Zschocke
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4. Marie-Luise Gross
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5. Kerstin Brismar
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6. Elisabete Forsberg
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Correspondence toVerena Peters.

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Peters, V., Schmitt, C.P., Zschocke, J. et al. Carnosine treatment largely prevents alterations of renal carnosine metabolism in diabetic mice.Amino Acids 42, 2411–2416 (2012). https://doi.org/10.1007/s00726-011-1046-4

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• Received: 13 April 2011
• Accepted: 15 July 2011
• Published: 11 August 2011
• Issue Date: June 2012
• DOI: https://doi.org/10.1007/s00726-011-1046-4

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