Low-dose streptozotocin induces sustained hyperglycemia in Macaca nemestrina

The potential for using macaques to create a nonhuman primate diabetic mode l M as investigated. The significant objectives were to determine a) progno sis of STZ induced permanent beta cell destruction in nonhuman primates. an d hi the potential to use STZ treated animals in a model of autoimmune diab etes by following adoptively transferred lymphocytes into MHC identical mac aques. Beta cell impairment was achieved by a single intravenous. low dose (10-40 mg/kg body weight) streptozotocin injection in a majority of pigtailed maca ques (Macacac nemestrinct) Multiple injections, even at low doses at close intervals affected liver and kidney functions in addition to beta cell dest ruction. Abnormal IVGTT were observed in all streptozotocin-treated animals , in some within ii week to 10 days. The fasting blood glucose levels rose from <70 mg/dl in pre-STZ stage to above 400 mg/dl in severely diabetic mac aques. Histological evidence suggests loss of beta cells when animals M ere euthanized within two to four weeks post-STZ treatment. Near complete dest ruction of beta cells was observed in animals maintained longer than three months on insulin. Donor T cells from STZ-treated animals were incubated ov ernight with 10 U/ml IL-2 and 2.5 <mu>g/ml PHA and then injected iv into a MHC-identical non-diabetic sibling, Three weeks later a second injection of donor PMBC labeled with vital dye Cell Tracker Green was given and the ani mal was euthanized after 24 hours. The recipient showed labeled donor T cel ls in the pancreas, spleen and peripheral blood, consistent with specific h oming of activated lymphocytes from the diabetic donor.