Controversy persists concerning the origin of insulin in the central n
ervous system. While there has been convincing evidence in vitro to de
monstrate the presence of neuronal insulin mRNA, conventional assays h
ave failed to detect the same in whole brain preparations. Here we emp
loyed RNAse-protection and sensitive reverse transcription-polymerase
chain reaction (RT-PCR) assays in attempts to detect insulin I and II
mRNAs in rat brains obtained from different developmental stages. The
RNAse-protection assay did not detect insulin I or insulin II transcri
pts in fetal (13 to 21 day gestation) or adult brains. RT-PCR, while d
etecting low amounts of insulin I transcripts in other extrapancreatic
tissues such as the rat yolk sac and fetal liver previously shown to
express insulin II, failed to detect insulin I in brain at any age exa
mined. Insulin II mRNA was detected by RT-PCR in fetal, neonatal and a
dult rat brains, just as in yolk sac, fetal and adult livers. We concl
ude that while the duplicated insulin I gene is not expressed, the anc
estral insulin II gene is expressed in fetal, neonatal and adult rat b
rains. Our observations support the concept of de novo brain insulin I
I synthesis beyond the pre-pancreatic stage of embryonic development.