The endocrine pancreas of the fetus from diabetic pregnant rat

Abstract

Diabetes was induced in female rats by streptozotocin administration prior to mating. Pregnant rats were divided into "severe diabetics" (blood glucose concentration above 300 mg/100 ml) and "mild diabetics" (blood glucose ranging from 100 to 200 mg/100 ml). When compared to control fetuses, fetuses from severely diabetic mothers showed a slight decrease of body weight on days 20.5 and 21.5. Fetal pancreatic insulin stores and plasma insulin concentrations were decreased at 19.5, 20.5 and 21.5 days. The insulin response to glucose was impaired both in vivo and in vitro. In contrast, fetuses from mildly diabetic females showed no change in body weight. Pancreatic and plasma insulin concentrations were increased at 19.5, 20.5 and 21.5 days. The response of the beta cells of term fetuses of mild diabetics to glucose stimulation was enhanced in vitro. These results are consistent with the hyperglycaemia-hyperinsulinaemia theory with regard to the fetuses from mildly diabetic rats and with an impairment of insulin biosynthesis and release in fetuses from severely diabetic females.

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype

“…This has been demonstrated in several studies using animal models (1,4,6,15,22). There were no significant changes in the total number of islets, percent distribution of large-and small-sized islets, or number of insulin-positive cells in pancreata from 2-HC fetuses (data not shown).…”

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

“…The very mild disturbance of basal blood glucose in the GK fetus is associated with growth retardation of the pancreas with poor development of the beta cells, a fetal pattern which is generally observed only in the context of severe diabetes with considerable hyperglycaemia and wasting of the mother (as obtained in spontaneous or streptozotocin diabetes or by glucose infusion) [29][30][31][32][33][34][35][36]. On the other hand, mild experimental diabetes during pregnancy in the rat has been reported to result in normal or even enhanced development of the fetal beta-cell mass [31,32,35]. Therefore the so far recognized notion that the degree of disturbance in the maternal (and fetal) metabolism is an important determinant of the amount of retardation of fetal beta-cell development does not apply to the GK model.…”

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

“…A severe hyperglycaemia ( > 20 mmol/1) in the maternal rat results in hyperglycaemia and hypoinsulinaemia of their fetuses. On histology and electronmicroscopy, we found evidence of islet hypertrophy, Beta-cell hyperplasia and Beta-cell degranulation in these fetuses: a 'Beta-cell exhaustion phenomenon' is probably the cause of decreased insulin levels in fetal serum [1,2]. Malnutrition of the newborn rats by their mothers, causes frequent postnatal death and subnormal glucose and insulin levels in the survivors until weaning [1,3].…”

“…Malnutrition of the newborn rats by their mothers, causes frequent postnatal death and subnormal glucose and insulin levels in the survivors until weaning [1,3]. Body weight in the offspring of severely hyperglycaemic rats is significantly lower than normal from day 20 of gestation and it remains significantly lower during postnatal life: during the lactation period and after weaning [1][2][3]. The adult offspring of severely hyperglycaemic pregnant rats (SDF-rats) have a normal pancreas on histology and normal serum glucose and insulin concentrations in basal conditions, but their glucose tolerance is clearly impaired [3,4].…”