The evolution of function and response to arginine challenge and pregnancy of portally and systemically placed islet cell grafts in streptozotocin diabetic mice

Abstract

Mice made diabetic with streptozotocin received organ cultured fetal islet cell grafts in the portal (PG) or systemic (SG) vascular beds in order to determine whether portal delivery of insulin is an important consideration in graft placement. Grafts were established more quickly in SG mice as shown by body weight and blood glucose estimations. Intraperitoneal arginine was found to be a stronger insulin secretagogue than intravenous glucose with the doses used when serum insulin was measured 5 minutes after injection. Glucose response to an arginine challenge was initially abnormal in both groups of mice, but was identical to normal controls 4 months after transplantation, showing that engraftment is a gradual process. Mice were then mated and their response to the chronic glycemic stress of pregnancy was noted. PG and SG mice had normal fertility rates in contrast to untreated diabetics, none of which became pregnant. Offspring were normal with respect to litter size, body weight, malformation rate, and pancreatic insulin content compared with historical controls. PG and SG mothers behaved normally during pregnancy, with the exception of a raised glycosylated hemoglobin level at day 19.5 gestation (5.5% and 5.5% v 3.7%, P < .01). We were, therefore, unable to detect any difference between portally and systemically placed islet grafts.