Effect of Ischemia and Temperature on Fetal Mouse Pancreas: Insulin Production In Vitro, and Function After Isotransplantation

Abstract

The effects of ischemia at varying temperatures on the survival of fetal islet endocrine cells was investigated by placing 17-day-old fetal mouse pancreata in organ culture after 2, 4, or 6 h at either 4°C, 22°C, or 37°C. Insulin secretion by the cells in vitro, the content of insulin in the cultured pancreata, and the ability of the cultured islets to reverse diabetes in syngeneic streptozotocin-diabetic mie were assessed. Fetal pancreas subjected to 2–6 h of ischemia at either 4°C or 22°C showed neither loss of insulin secretory capacity in vitro nor loss of ability to produce large functional grafts, and behaved identically to tissue not subjected to deliberate ischemia. In contrast, after 2 h of ischemia at 37°C, although some grafts functioned, their insulin content was reduced despite apparently normal prior insulin production in vitro, but 4 or 6 h at 37°C resulted in total loss of functional islet tissue. However, despite retention of functional capacity and the ability to produce large grafts with high insulin content after cold or room temperature ischemia, some loss of insulin storage capacity in vitro was noted by islets subjected to ischemie periods longer than 2 h even at 4°C. Thus, fetal pancreas can withstand prolonged periods of ischemia provided its temperature is reduced, and functional recovery can be demonstrated after transplantation.