Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy.

During gestation the demand for insulin increases due to a decrease in insulin sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell proliferation, as well as insulin production and secretion increase. Both phenomena appear to be caused by the actions of pregnancy hormones. We studied the relationship between the two phenomena by investigating whether the supply of exogenous insulin affects the secretion of pregnancy hormones and islet function during gestation. For that purpose rats were treated with high doses of insulin (4.8 IU day-1 by sub-cutaneous osmotic mini pumps) so that the endogenous demand for insulin was fully satisfied from day 8-14 of gestation. Euglycaemia (5.0 mM) was maintained by intra venous infusion of glucose. The treatment suppressed insulin synthesis, as measured by in situ hybridization, in both pregnant and cyclic rats. In addition, in pregnant rats the increments in insulin secretion and in islet-cell proliferation were partly prevented. Furthermore, the data also suggest that in pregnant rats the treatment partly prevented the decrease in insulin sensitivity. Finally, the treatment did not affect the plasma concentrations of progesterone, prolactin and placental lactogen, but prevented the rise in growth hormone concentrations in pregnant rats. The present data suggest that, next to direct effects of pregnancy hormones and growth hormone on the pancreatic islets, a decreased insulin sensitivity in the maternal tissues, induced by actions of the same hormones, is involved in the regulation of islet function during gestation.