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Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

An Erratum to this article was published on 09 July 2005

Abstract

Purpose

Cardiac scintigraphic studies using 123I-labeled metaiodobenzylguanidine ([123I]MIBG) have demonstrated heterogeneous myocardial accumulation of MIBG in diabetes. The accumulation has been found to correlate with a heterogeneous decrease in the expression of norepinephrine transporter (NET). In diabetic peripheral nerve tissue, polyol pathways are activated and cause nerve dysfunction and degeneration. However, there has been little research on the polyol pathway and cardiac sympathetic nerves. Therefore, to assess the influence of the polyol pathway on cardiac sympathetic nervous function, we investigated the regional accumulation of MIBG and NET protein expression in diabetic model rats treated with aldose reductase inhibitor (ARI) for the blockade of polyol pathways.

Methods

Rats were given a single intravenous injection of streptozotocin (n=76, STZ-D rats). Starting the day after STZ injection, ARI was administered daily to 42 of the rats for 4 weeks (ARI-D rats). To assess the cardiac sympathetic nervous function, [125I]MIBG autoradiographic experiments were carried out. Finally, NET protein expression was assessed with a saturation binding assay.

Results

The myocardial sorbitol concentration was significantly higher in STZ-D rats than in ARI-D rats. There was no heterogeneous accumulation of MIBG in ARI-D rats. There was a heterogeneous decrease of NET expression in STZ-D rats, but not in ARI-D or control rats.

Conclusion

The gathered data indicate that the enhanced polyol pathway correlates with the decrease in regional cardiac sympathetic nervous function, and this impairment may lead to the reduction of NET protein in cardiac sympathetic nerves of the diabetic inferior wall.

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Acknowledgments

This study was supported in part by Grants-in-Aid for General Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science”. We would like to thank Daiichi Radioisotope Laboratories Ltd., Tokyo, Japan, for providing [125I]MIBG, and Ono Pharmaceutical Co., Ltd., Osaka, Japan for providing epalrestat.

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Authors and Affiliations

  1. Radioisotopes Research Laboratory, Hospital, Faculty of Medicine, Kyoto University, Kyoto, 606-8507, Japan

    Yasushi Kiyono

  2. Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Satomi Kajiyama, Hiromi Fujiwara, Naoki Kanegawa & Hideo Saji

Authors
  1. Yasushi Kiyono
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  2. Satomi Kajiyama
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  3. Hiromi Fujiwara
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  4. Naoki Kanegawa
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  5. Hideo Saji
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Corresponding author

Correspondence to Hideo Saji.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00259-005-1865-1

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Kiyono, Y., Kajiyama, S., Fujiwara, H. et al. Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG. Eur J Nucl Med Mol Imaging 32, 438–442 (2005). https://doi.org/10.1007/s00259-004-1694-7

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  • DOI: https://doi.org/10.1007/s00259-004-1694-7

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