Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective β cell destruction

Takimoto, Glenn S.; Jones, Carl W.; Lands, William E.M.; Bauman, Anne; Jeffrey, J; Jonasson, Olga

doi:10.1016/0026-0495(88)90137-0

Cited by 16 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In nonhuman primates a dose level of 100-150 mg/kg is generally recommended to ensure reproducible induction of diabetes. At lower dose levels variable results are obtained: Koulmanda et al (2003) observed successful induction of diabetes for a 55 mg/kg dose, while others reported diabetes in only half of animals at that dose level (Takimoto et al, 1988). In our experience the 150 mg/kg dose invariably resulted in long-lasting diabetes, with only rarely limiting side effects.…”

Section: Discussionmentioning

confidence: 79%

Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

et al. 2005

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 79%

Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

et al. 2005

View full text Add to dashboard Cite

“…Larger doses of 100 to 150 mg/kg were found sufficient 16,18,23 but were associated with more adverse effects and complications. 16Y19,23 In contrast, Koulmanda et al 16 reported that 55 mg/kg was sufficient to consistently induce diabetes in cynomolgus monkeys, but others have been less successful with this dosage, 17,21,24,25 with C-peptide production still detectable (in the range of 0.6Y0.9 ng/mL). Wijkstrom et al 23 suggested that the dose should be based on body surface area (1250 mg/m 2 ) rather than body weight.…”

Section: Discussionmentioning

confidence: 84%

“…Such a response has been described in rodents 26,27 and monkeys. 24,28 Interpretation of the triphasic response is that there is an initial decrease of insulin release as a result of inflammation and an inability of the beta cells to respond to glucose because of impaired glucose oxidation in the beta cell; 15,27 this explains the initial rise in blood glucose (phase 1). Further destruction and disruption of the beta cells results in a massive release of insulin leading to a fall in blood glucose level (phase 2).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Diabetes in Cynomolgus Monkeys With High-dose Streptozotocin

Rood¹,

Bottino²,

Balamurugan³

et al. 2006

Pancreas

View full text Add to dashboard Cite

show abstract

“…The resistance of nude mice and thymectomized mice to STZ (Paik et al 1980) and the results of adoptive transfer experiments (Buschard and Rygaard 1977) and reconstitution experiments (Paik et al 1982;Paik et al 1980) all support a role of T cells in the development of diabetes after low-dose STZ. In an effort to recapitulate this model in macaques, several investigators (Gaur et al 2001;McCulloch et al 1991;Takimoto et al 1988) have used single to multiple low-dose STZ treatment in macaques and baboons to achieve beta-cell destruction.…”

Section: Use Of Stzmentioning

confidence: 98%

Nonhuman Primate Models for Islet Transplantation in Type 1 Diabetes Research

Gaur¹

2004

ILAR Journal

View full text Add to dashboard Cite

Insulin-dependent diabetes mellitus is an autoimmune disease that causes a progressive destruction of the pancreatic beta cells. As a result, the patient requires exogenous insulin to maintain normal blood glucose levels. Both the pancreas and the islets of Langerhans have been transplanted successfully in humans and in animal models, resulting in full normalization of glucose homeostasis. However, insulin independence, transient or persistent, was documented in only a small fraction of cases until recently. The chronic immunosuppression required to avoid immunological rejection appears to be toxic to the islets and adds the risk of lymphoproliferative disease reported earlier. For islet transplantation to become the method of choice, it is essential first to identify islet-friendly immunosuppressive regimens and/or to develop methods that induce donor-specific tolerance and improve islet isolation and transplantation protocols. Indeed, researchers have already successfully allografted islets in the presence of nonsteroidal immunosuppression in a process known as the Edmonton protocol. An alternative method, gene therapy, could replace these other methods and better meet the insulin requirement of an individual without requiring pancreatic or islet transplantation. This alternative, however, requires animal models to develop and test clinical protocols and to demonstrate the feasibility of preclinical trials. Nonhuman primates are ideally suited to achieve these goals. The efforts toward developing a nonhuman primate diabetic model with demonstrable insulin dependence are discussed and include pancreatic and islet transplant trials to reverse the diabetic state and achieve insulin independence. Also described are the various protocols that have been tested in primates to circumvent immunosuppression by using tolerance induction strategies in lieu of immunosuppression, thus exploring the field of donor-specific tolerance that extends beyond islet transplantation.

show abstract

Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective β cell destruction

Cited by 16 publications

References 19 publications

Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

Induction of Diabetes in Cynomolgus Monkeys With High-dose Streptozotocin

Nonhuman Primate Models for Islet Transplantation in Type 1 Diabetes Research

Contact Info

Product

Resources

About