Gestational hyperglycaemia and insulin release by the fetal rat pancreas in vitro: effect of amino acids and glyceraldehyde.

Unrestrained pregnant rats were infused with glucose during the last week of pregnancy to produce slight or high gestational hyperglycaemia. Control rats were infused with distilled water. Insulin secretion of the fetuses at term was studied in vitro using a perifusion system. Compared with controls, perifused pancreases of slightly hyperglycaemic fetuses showed a similar pattern of insulin secretion in response to 10 mmol/l leucine. Arginine-induced insulin secretion at 20 mmol/l was higher than in controls. In both groups, 10 mmol/l alpha-ketoisocaproate had a poor stimulatory effect on insulin release, and 5 mmol/l D-glyceraldehyde was ineffective in eliciting insulin secretion. In highly hyperglycaemic fetuses all the secretagogues, with the exception of arginine, which induced a sustained monophasic insulin secretory response, had no effect on insulin release. These data show that long-term exposure of fetal B cells to high plasma glucose levels in utero suppresses or alters further insulin secretory response not only to glucose but also to other nutrient secretagogues. The partially spared insulin secretory response to arginine suggests that the defect may concern stimulus-secretion coupling rather than insulin releasing machinery.