Extrapancreatic insulin gene expression in the fetal rat.

Analysis of gene expression in rat yolk sac, a primitive endodermal structure, revealed a low level of developmentally regulated insulin production. At 14 days of gestation, a 2.4-kilobase (kb) RNA species hybridized to cloned insulin gene probes. This species increased throughout gestation. At 16 days, a second transcript of 0.72 kb became visible and, by 18 days, the 0.72-kb transcript predominated. In the pancreas, the fully processed insulin mRNA is 0.55 kb long. Over the same time period in the fetal liver (also a tissue of endodermal origin, as is the pancreas), only the 2.4-kb transcript was detected; no hybridizing transcripts were detected in adult liver RNA. Gel filtration studies and insulin radioimmunoassay of acid/ethanol-soluble peptides showed approximately equal amounts of proinsulin and insulin in 18-day yolk sac, a result suggesting that the transcripts in this tissue are translated. On the other hand, a lower level of insulin and the lack of proinsulin in fetal liver were compatible with a pancreatic origin of hepatocyte insulin by receptor binding rather than intrahepatic insulin synthesis.