Sulfonylurea and glinide drugs display different effects on insulin granule motion in single β-cells in vitro. We therefore investigated the different effects that these drugs manifest towards insulin release in an in vivo long-term treatment model. Diabetic GK (Goto-Kakizaki) rats were treated with nateglinide, glibenclamide or insulin for 6 weeks. Insulin granule motion in single β-cells and the expression of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins were then analysed. Perifusion studies showed that decreased first-phase insulin release was partially recovered when GK rats were treated with nateglinide or insulin for 6 weeks, whereas no first-phase release occurred with glibenclamide treatment. In accord with the perifusion results, TIRF (total internal reflection fluorescence) imaging of insulin exocytosis showed restoration of the decreased number of docked insulin granules and the fusion events from them during first-phase release for nateglinide or insulin, but not glibenclamide, treatment; electron microscopy results confirmed the TIRF microscopy data. Relative to vehicle-treated GK β-cells, an increased number of SNARE clusters were evident in nateglinide- or insulin-treated cells; a lesser increase was observed in glibenclamide-treated cells. Immunostaining for insulin showed that nateglinide treatment better preserved pancreatic islet morphology than did glibenclamide treatment. However, direct exposure of GK β-cells to these drugs could not restore the decreased first-phase insulin release nor the reduced numbers of docked insulin granules. We conclude that treatment of GK rats with nateglinide and glibenclamide varies in long-term effects on β-cell functions; nateglinide treatment appears overall to be more beneficial.
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Research Article|
April 25 2008
Insulin exocytosis in Goto-Kakizaki rat β-cells subjected to long-term glinide or sulfonylurea treatment
Junko Kawai;
Junko Kawai
*Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
†Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, 113–8421, Japan
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Mica Ohara-Imaizumi;
Mica Ohara-Imaizumi
*Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Yoko Nakamichi;
Yoko Nakamichi
*Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Tadashi Okamura;
Tadashi Okamura
‡Division of Animal Models, Department of Infectious Diseases, Research Institute, International Medical Center of Japan, Tokyo 162–8655, Japan
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Yoshihiro Akimoto;
Yoshihiro Akimoto
§Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Satsuki Matsushima;
Satsuki Matsushima
∥Department of Clinical Pathology, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Kyota Aoyagi;
Kyota Aoyagi
*Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Hayato Kawakami;
Hayato Kawakami
§Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Takashi Watanabe;
Takashi Watanabe
∥Department of Clinical Pathology, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
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Hirotaka Watada;
Hirotaka Watada
†Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, 113–8421, Japan
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Ryuzo Kawamori;
Ryuzo Kawamori
†Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, 113–8421, Japan
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Shinya Nagamatsu
Shinya Nagamatsu
1
*Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181–8611, Japan
1To whom correspondence should be addressed (email shinya@kyorin-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
September 18 2007
Revision Received:
January 30 2008
Accepted:
February 06 2008
Accepted Manuscript online:
February 06 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 412 (1): 93–101.
Article history
Received:
September 18 2007
Revision Received:
January 30 2008
Accepted:
February 06 2008
Accepted Manuscript online:
February 06 2008
Citation
Junko Kawai, Mica Ohara-Imaizumi, Yoko Nakamichi, Tadashi Okamura, Yoshihiro Akimoto, Satsuki Matsushima, Kyota Aoyagi, Hayato Kawakami, Takashi Watanabe, Hirotaka Watada, Ryuzo Kawamori, Shinya Nagamatsu; Insulin exocytosis in Goto-Kakizaki rat β-cells subjected to long-term glinide or sulfonylurea treatment. Biochem J 15 May 2008; 412 (1): 93–101. doi: https://doi.org/10.1042/BJ20071282
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