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Augmented β cell loss and mitochondrial abnormalities in sucrose-fed GK rats

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Abstract

Progressive decline of islet β cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model. Six-week-old male GK rats were given 30% sucrose orally for 2 weeks. Normal Wistar rats fed with sucrose served as controls. Compared to untreated GK rats, sucrose-fed GK rats showed severe degeneration and death of β cells with disrupted and swollen mitochondria and a greater β cell loss. Submicroscopic analysis disclosed a smaller mean volume and a greater number of mitochondria in β cells in GK rats compared to those in Wistar rats. Mitochondria in sucrose-fed GK rats were 2.4-fold greater in mean volume than those in untreated state. Without sucrose feeding, there was no significant difference in mitochondrial membrane potentials (MmPs) of isolated islets between Wistar and GK rats. MmPs were reduced by 44% in sucrose-fed GK rats but not influenced in sucrose-fed Wistar rats. Current results suggest that nutritional insults like sucrose feeding may exert deleterious effects on mitochondria, resulting in augmented β cell loss in type 2 diabetes.

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Acknowledgment

This study was not possible without the kind supply of GK rats from Drs. Hitoshi Ikeda and Hiroyuki Odaka, Research Institute, Takeda Pharmaceuticals. The authors are indebted to Ms. Yuko Sasaki for her expert technical assistance. This study was supported by grants to Soroku Yagihashi from the Ministry of Education, Science, Sports and Culture, Japan.

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Authors and Affiliations

  1. Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Hiroki Mizukami, Ryuichi Wada, Motoi Koyama & Soroku Yagihashi

  2. Department of Physiology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Teruko Takeo, Sechiko Suga & Makoto Wakui

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  1. Hiroki Mizukami
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  2. Ryuichi Wada
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  7. Soroku Yagihashi
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Correspondence to Soroku Yagihashi.

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Mizukami, H., Wada, R., Koyama, M. et al. Augmented β cell loss and mitochondrial abnormalities in sucrose-fed GK rats. Virchows Arch 452, 383–392 (2008). https://doi.org/10.1007/s00428-007-0508-2

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