Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys

Mark D Stegall, J. Chabot, C. Weber, K. Reemtsma, M. A. Hardy

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Abstract

Using a model of streptozotocin-induced, ketosisprone, insulin-dependent diabetes mellitus (IDDM) in the cynomolgus monkey, we performed 11 intraportal transplants of collagenase-digested, Ficoll-purified pancreatic islets (9 ABO-compatible allografts and 2 concordant baboon xenografts). Islets were pretreated with ultraviolet-B irradiation and recipients received cyclosporine A immunosuppression. Two grafts never functioned, five grafts showed evidence of partial function, and four grafts (three allografts and one xenograft) showed evidence of good function, with the animals independent of exogenous insulin with morning fasting blood glucose levels less than 200 mg/dl. Because two grafts functioned only after CsA was either tapered or discontinued, we performed a related study that showed that therapeutic doses of CsA (morning trough serum level 150-250 ng/ml) impaired intravenous glucose tolerance tests (IVGTT) of normal monkeys and may contributed to graft dysfunction in our islet transplantation model. The results show that there is a decrease in release of serum insulin during an IVGTT leading to impairment of glucose utilization, while serum glucagon remains unaffected. After cessation of CsA, the IVGTT did not return to normal for 28 days. Oral glucose tolerance tests were unaffected in CsA-treated monkeys. These initial studies show that the streptozotocin-diabetic monkey is a valuable model to study IDDM and islet transplantation in nonhuman primates. We also confirm studies in rodents, dogs, and sheep by showing that CsA partially inhibits beta cell function in normal monkeys.

Original languageEnglish (US)
Pages (from-to)944-950
Number of pages7
JournalTransplantation
Volume48
Issue number6
StatePublished - 1989
Externally publishedYes

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Islets of Langerhans Transplantation
Macaca fascicularis
Cyclosporine
Haplorhini
Glucose Tolerance Test
Transplants
Glucose
Streptozocin
Type 1 Diabetes Mellitus
Heterografts
Allografts
Serum
Insulin
Ficoll
Glucose Intolerance
Papio
Collagenases
Glucagon
Islets of Langerhans
Immunosuppression

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys. / Stegall, Mark D; Chabot, J.; Weber, C.; Reemtsma, K.; Hardy, M. A.

In: Transplantation, Vol. 48, No. 6, 1989, p. 944-950.

Research output: Contribution to journalArticle

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