The effect of streptozotocin on the function of fetal porcine and rat pancreatic (pro-)islets^*

Summary

Streptozotocin (STZ) is a broad spectrum antibiotic with anti-tumor and diabetogenic properties. Although STZ has been studied for many years, the exact mechanism of its diabetogenic action has not yet been fully elucidated. The present study investigated the effect of STZ on both fetal porcine proislets (FPP) and fetal rat islets (FRI) in an attempt to elucidate the diabetogenic effect of STZ on fetal pancreatic beta cells. This study demonstrates that after in vitro exposure of both FPP and FRI for 30 min to 2.2 mM and 4.4 mM STZ, respectively, FPP showed microscopically an intact structure, a spherical shape and a translucent color, while, in contrast, most FRI were disrupted and showed a slight white color with dark centers. Based on these data, we first transplanted FPP and FRI beneath the renal capsules of nude mice. Three to four weeks later, a single dosage of streptozotocin (180 mg/kg) was intravenously administered. Six of the seven nude mice pre-transplanted with FPP became diabetic (blood glucose, BG, 308.08 ± 33.62 mg/dl) within 2 — 5 days and then gradually achieved normoglycemia 51.56 ± 7.71 days after STZ injection. After removal of the grafts, all of the six diabetic mice with normoglycemia returned to hyperglycemia (BG > 300 mg/dl). In contrast, all of the five nude mice pretransplanted with FRI persistently maintained hyperglycemia (BG > 300 mg/dl) and died 5 ±0.84 days after STZ injection. In control groups rendered diabetic by STZ, all 7 diabetic mice transplanted with FRI returned to normoglycemia within 1 — 2 days and another 5 diabetic mice without transplantation remained hyperglycemic and died within 10 ± 2.4 days. The data presented here demonstrate that FPP are insensitive to the diabetogenic effect of STZ, in contrast to FRI which are sensitive. This study is valuable in developing an optimal procedure to induce diabetes in animals to examine the in-vivo potential of immature fetal islets to reverse diabetes and to elucidate the mechanism of the diabetogenic effect of STZ.

Key words

Streptozotocin - fetal porcine proislets - fetal rat islets - transplantation