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, pancreat ic islet-cell proliferation, as well as insulin production and secreti on increase. Both phenomena appear to be caused by the actions of preg nancy hormones. We studied the relationship between the two phenomena by investigating whether the supply of exogenous insulin affects the s ecretion of pregnancy hormones and islet function during gestation. Fo r that purpose rats were treated with high doses of insulin (4.8 IU da y(-1) by sub-cutaneous osmotic mini pumps) so that the endogenous dema nd for insulin was fully satisfied from day 8-14 of gestation. Euglyca emia (5.0 mM) was maintained by intra venous infusion of glucose. The treatment suppressed insulin synthesis, as measured by in situ hybridi zation, in both pregnant and cyclic rats. In addition, in pregnant rat s the increments in insulin secretion and in islet-cell proliferation were partly prevented. Furthermore. the data also suggest that in preg nant rats the treatment partly prevented the decrease in insulin sensi tivity. Finally, the treatment did not affect the plasma concentration s of progesterone, prolactin and placental lactogen, but prevented the rise in growth hormone concentrations in pregnant rats. The present d ata suggest that, next to direct effects of pregnancy hormones and gro wth hormone on the pancreatic islets, a decreased insulin sensitivity in the maternal tissues, induced by actions of the same hormones, is i nvolved in the regulation of islet function during gestation.