Effect of maternal hyperglycaemia on insulin secretion by monolayer cultures of pancreatic cells from neonatal rats: a perifusion study.

The effect of maternal hyperglycaemia on the function of neonatal B cells was examined using a perifusion technique in pancreatic monolayer cultures of neonatal rats from normoglycaemic mothers (C), and those made slightly hyperglycaemic (SH) and highly hyperglycaemic (HH) by injection of streptozotocin. Monolayer cultures were kept for 7 days in medium containing 5.5 mmol glucose/1 plus 1 mmol 2-deoxy-glucose/1. On day 0, B cells in the C group responded to 16.7 mmol glucose/1, 10 mmol leucine/1 and 10 mmol 2-ketoisocaproate/1 in a monophasic fashion with no significant rise in the second phase. However, compared with the C group, a significant increase in the second-phase secretion in response to glucose and 2-ketoisocaproate was observed in the SH group, although there was no difference in the first-phase secretion. In the HH group the insulin secretion was lower in the first phase but not in the second phase. After culture for 7 days, B cells in the C group showed a biphasic response to the secretagogues, with a great increase in the second-phase secretion. In the SH group, the second phase of insulin secretion was increased but the increment was far less than that in the C group. The secretory response was remarkably low in the HH group compared with other groups. From these results, we conclude that at an early stage of culture slight maternal hyperglycaemia causes a hypersensitivity of neonatal B cells but impairs the normal development of the function of B cells during culture, and that high hyperglycaemia results in impaired insulin secretion throughout the whole period of culture studied.