Protein-caloric food restriction affects insulin-like growth factor system in fetal Wistar rat.
We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 d post coitum exhibit increased beta-cell mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern similar to that reported in infants of mild diabetic mothers. In this work, we investigated in undernourished fetuses: 1) whether availability of growth factors such as insulin, GH, and IGFs and their binding proteins (IGFBPs) could be implicated in this alteration, and 2) the beta-cell mitogenic response to IGFs in vitro. The results show that maternal undernutrition increases pancreatic IGF-I expression and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I expression and serum IGF-I levels were decreased. No changes were observed in serum IGF-II, and its expression was diminished in undernourished pancreases and unchanged in the liver, compared with control fetuses. Serum levels and liver and pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in pancreas were increased. Finally, the beta-cell mitogenic response to IGFs in vitro was significantly increased in undernourished fetal islets, compared with controls. In conclusion, in undernourished fetuses the increased beta-cell mass can be related to the stimulation of replicative beta-cell response due to locally increased pancreatic IGF-I mRNA; this effect is perhaps potentiated or favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene expression.
Martín
M A
MA
Instituto de Bioquímica, Consejo Superior de Investigaciones Cientificas Universidad Complutense de Madrid, Facultad de Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain.
Serradas
P
P
Ramos
S
S
Fernández
E
E
Goya
L
L
Gangnerau
M N
MN
Lacorne
M
M
Pascual-Leone
A M
AM
Escrivá
F
F
Portha
Bernard
B
Alvarez
C
C
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002149:Energy Intake; D005260:Female; D005333:Fetus / Q000378:metabolism; D005508:Food Deprivation; D006133:Growth Substances; D007328:Insulin / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007515:Islets of Langerhans / Q000196:embryology / Q000378:metabolism; D010179:Pancreas / Q000196:embryology; D011247:Pregnancy; D011270:Pregnancy, Animal; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012260:Ribonucleases / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*; D013997:Time Factors
D006133:Growth Substances; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D013002:Somatomedins; D012313:RNA; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012260:Ribonucleases; D001973:Bromodeoxyuridine