Ag. Nieuwenhuizen et al., ROLE OF INCREASED INSULIN DEMAND IN THE ADAPTATION OF THE ENDOCRINE PANCREAS TO PREGNANCY, Acta Physiologica Scandinavica, 159(4), 1997, pp. 303-312
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.