Resistance of the human fetal beta-cell to the toxic effect of multiple low-dose streptozotocin.
The human fetal beta-cell is different from the adult beta-cell not only in that it is unable to release significant amounts of insulin during an acute glucose challenge, but also in that it is resistant to the toxic effects of a bolus of streptozotocin (STZ) and chronic exposure to cytokines tumour necrosis factor-alpha and interferon-gamma. To examine further the differences between the immature and mature beta-cell, these cells were exposed to multiple low doses of STZ (MLS) both in vivo and in vitro, the regimen used being classically toxic to rodent adult beta-cells. The in vivo experiments were conducted after the tissue had been grafted into the athymic mouse. There was no adverse effect of MLS on the insulin content of engrafted human fetal pancreatic explants, either 1, 4, or 15 weeks after the injection of 70 mg/kg/i.p. STZ daily for 5 days. Diabetes, induced in the mice by MLS or a bolus of STZ, was reversed in five of seven MLS-treated mice at 59 +/- 8 days and four of seven STZ-treated animals at 75 +/- 10 days (no significant difference). The growth rate of the implanted tissues also was not adversely affected by the MLS, nor was the percentage of beta-cells 2 weeks after completion of the MLS. In contrast, mouse fetal beta-cells transplanted into the athymic mouse were adversely affected, their insulin content 2 weeks after MLS being only 0.7% that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Tuch
B E
BE
Department of Medicine, University of Sydney, New South Wales, Australia.
Chen
J
J
D000818:Animals; D004351:Drug Resistance; D005260:Female; D016332:Fetal Tissue Transplantation; D005333:Fetus / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D011247:Pregnancy; D013311:Streptozocin / Q000633:toxicity*; D014183:Transplantation, Heterologous
D007328:Insulin; D013311:Streptozocin