title: Induction of insulin-dependent diabetes mellitus by total pancreatectomy for pancreatic islet transplantation in cynomolgus monkeys.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of General Surgery, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tomomi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yamashita
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Koshizuka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kuraya
authors.forename: Masaomi
authors.initials: M
authors.lastname: Ogura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamachi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Satoru
authors.initials: S
authors.lastname: Todo
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008252:Macaca fascicularis; D008297:Male; D010180:Pancreatectomy / Q000009:adverse effects*; D016896:Treatment Outcome