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 number and size of beta cells and enhanced gap-junctional coupling among beta cells, increased glucose-induced insulin response and decreased glucose stimulation threshold. The role exerted by pregnancy steroids and lactogenic hormones in the development of islets upregulation during pregnancy has been widely investigated. In the present study we studied the possibility that pregnancy steroids induce functional modifications of beta cells involving the expression and function of glucokinase. Our results indicate that estradiol and progesterone do not influence 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 increased glucose-induced insulin release. Therefore it is possible to hypothesize 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.
Magnaterra
R
R
Department of Internal Medicine, University of Rome Tor Vergata, Italy.
Porzio
O
O
Piemonte
F
F
Bertoli
A
A
Sesti
G
G
Lauro
D
D
Marlier
L N
LN
Federici
G
G
Borboni
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology*; D008954:Models, Biological; D010190:Pancreatic Neoplasms; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D007328:Insulin; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D005941:Glucokinase; D005947:Glucose