THE EFFECTS OF PREGNANCY STEROIDS ON ADAPTATION OF BETA-CELLS TO PREGNANCY INVOLVE THE PANCREATIC GLUCOSE SENSOR GLUCOKINASE

Pregnancy is associated with adaptive changes including increased numb er and size of beta cells and enhanced gap-junctional coupling among b eta cells, increased glucose-induced insulin response and decreased gl ucose stimulation threshold. The role exerted by pregnancy steroids an d lactogenic hormones in the development of islets upregulation during pregnancy has been widely investigated. In the present study we studi ed the possibility that pregnancy steroids induce functional modificat ions of beta cells involving the expression and function of glucokinas e. Our results indicate that estradiol and progesterone do not influen ce significantly glucokinase mRNA expression, while they induce a dose -dependent and time-dependent increase of glucokinase activity in RIN 1046-38 cells. The increased enzymatic activity results in an increase d glucose-induced insulin release. Therefore it is possible to hypothe size that pregnancy steroids influence glucokinase expression in beta cells at a post-transcriptional level and that this effect contributes to the development of hyperinsulinemia during pregnancy.