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Induction of insulin-dependent diabetes mellitus by total pancreatectomy for pancreatic islet transplantation in cynomolgus monkeys

  • Original article
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Background/purpose

In order to perform a preclinical trial of pancreatic islet transplantation (PIT) in nonhuman primates, insulin-dependent diabetes mellitus (IDDM) must be induced. Methods for IDDM induction are administration of streptozotocin (STZ) or total pancreatectomy (TP). While STZ-induced IDDM is not always reliable, TP is appropriate for IDDM induction. However, TP is very difficult because of the complex surgical procedure required, necessary confirmation of IDDM, and difficulty in postoperative management. In this study, we tried to establish a reliable IDDM model for PIT in cynomolgus monkeys.

Methods

TP was performed in 5 male cynomolgus monkeys (Macaca fascicularis). This was followed by scheduled measurements of blood glucose, C-peptide levels, insulin levels, oral intake, and insulin requirements. IDDM induction was confirmed by serum C-peptide levels and intravenous glucose tolerance test (IVGTT). Allogeneic PIT was performed 14 days later with immunosuppressive therapy.

Results

TP successfully induced IDDM in all animals, confirmed by reduction of fasting serum C-peptide levels. Negative responses of serum C-peptide levels and insulin in IVGTT provided further confirmation of IDDM induction. No mortality or morbidity was encountered in any of the animals.

Conclusions

TP successfully induced IDDM for PIT in cynomolgus monkeys.

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Acknowledgments

The authors thank Mr. R. Mitsuo and Mr. T. Nakamura for study conduction and Ms. M. Arako, Mr. J. Kimura, and others at SNBL for the excellent animal care. This work was supported in part by grants from Kyowa Hakko Kirin Co., Ltd. and Astellas Pharma Inc.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of General Surgery, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Tadashi Yoshida, Tomomi Suzuki, Masaaki Watanabe, Kenichiro Yamashita, Yasuyuki Koshizuka, Daisuke Kuraya, Masaomi Ogura, Hirofumi Kamachi, Michiaki Matsushita & Satoru Todo

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  1. Tadashi Yoshida
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  2. Tomomi Suzuki
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  3. Masaaki Watanabe
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  4. Kenichiro Yamashita
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  5. Yasuyuki Koshizuka
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  7. Masaomi Ogura
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Correspondence to Satoru Todo.

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Yoshida, T., Suzuki, T., Watanabe, M. et al. Induction of insulin-dependent diabetes mellitus by total pancreatectomy for pancreatic islet transplantation in cynomolgus monkeys. J Hepatobiliary Pancreat Sci 19, 661–666 (2012). https://doi.org/10.1007/s00534-011-0485-3

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  • DOI: https://doi.org/10.1007/s00534-011-0485-3

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