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1 Harvard Medical School
2 Massachusetts General Hospital
* To whom correspondence should be addressed. E-mail: lynn_wachtman{at}hms.harvard.edu.
Diabetes is a growing public health concern and animal models of this disease are necessary to fully understand disease pathogenesis, progression, clinical sequelae, and treatment options. In particular, non-human primate models of diabetes are important due to their close genetic relationship to humans. While numerous old-world primate models have been described, there are few studies examining the possibility of using new-world monkeys as an animal model for this disease. Streptozotocin is a common diabetogenic drug that selectively destroys beta cells after uptake via the GLUT2 glucose transporter. Induction of diabetes using streptozotocin was attempted in common marmosets (Callithrix jacchus). These animals showed increases in blood glucose consistent with diabetes only at STZ doses markedly greater than those used in other primate species. Additionally, all animals showed pathologic evidence of acute renal and liver toxicity secondary to the treatment. A comparative study of various non-human primates using GLUT2 immunostaining in pancreatic islets as a marker for sensitivity to STZ was subsequently performed. Immunostaining of islets from a variety of non-human primate species indicated a reduced expression of pancreatic GLUT2 in new-world monkeys compared to old-world monkeys which explains their resistance to diabetic induction with STZ. Further, there were age dependent differences in GLUT2 expression with both aged and infant macaques showing reduced expression. We conclude that new-world monkeys are an inappropriate model for diabetes induction with STZ and that with all primate species it is important to consider the animals' age before attempting diabetic induction with STZ.
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