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Induction of insulin‐dependent diabetes mellitus by total pancreatectomy for pancreatic islet transplantation in cynomolgus monkeys
Author(s) -
Yoshida Tadashi,
Suzuki Tomomi,
Watanabe Masaaki,
Yamashita Kenichiro,
Koshizuka Yasuyuki,
Kuraya Daisuke,
Ogura Masaomi,
Kamachi Hirofumi,
Matsushita Michiaki,
Todo Satoru
Publication year - 2012
Publication title -
journal of hepato‐biliary‐pancreatic sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 1868-6974
DOI - 10.1007/s00534-011-0485-3
Subject(s) - medicine , diabetes mellitus , islet , insulin , streptozotocin , endocrinology , pancreatectomy , transplantation , c peptide , pancreas transplantation , pancreas , insulin dependent diabetes , autoimmune disease , disease , kidney transplantation
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.