In rodents, the first insulin-producing cells appear in the pancreas at mid-gestation around embryonic day 11 (E11). However, on the basis of various features, such as morphology or hormonal coexpression, it is apparent that these initial insulin-expressing cells are different from those that develop after E15. In the present study, the pancreatic expression of both thyrotropin-releasing hormone (TRH) mRNA and insulin was studied during embryonic and fetal life. We report here that in the rat, while insulin mRNA is detected in the pancreas as early as E12, TRH mRNA cannot be detected before E16. At that stage and later on during fetal and early postnatal life, TRH mRNA is detected in insulin-producing cells, no signal being detected in other endocrine cell types or in exocrine tissue. It was also noted, by means of triple staining performed at E17, that the expression of TRH mRNA was restricted to insulin-expressing cells negative for glucagon, whereas the few insulin-expressing cells present at that stage, which coexpress insulin and glucagon, did not express TRH mRNA. Taken together, these data indicate that TRH is a marker of insulin-expressing cells, which develop after E15.
A Basmaciogullari, C Cras-Meneur, P Czernichow and R Scharfmann
G Skoglund, A Basmaciogullari, B Rouot, JC Marie and G Rosselin
G protein alpha-subunits are involved in the transduction of receptor-mediated regulation of insulin and glucagon secretions. To get further insight into the status of G proteins in alpha- and beta-cells of the Langerhans islets, we have used immunohistochemistry to study the distribution of alpha-subunits in pancreas sections from the rat. Our results show that only insulin-immunoreactive beta-cells display immunoreactivity for selective antibodies directed against the different members of the Galphas and Galpha12-families (alphas, alphaolf, and alpha12, alpha13 respectively). Immunoreactivities for antibodies directed against members of the Galphaq- and Galphai-families showed a more diverse localization: alpha11 and alphao2 were only detected in glucagon-immunoreactive alpha-cells, whereas alphai1 was detected in all beta-cells but only in a few alpha-cells. Even though beta-cells showed immunoreactivities for alphao-non-isoform-selective antibodies, we could not identify the isoform(s) present using selective alphao1 and alphao2 antibodies. Other members of the Galphai- and Galphaq-families (alphai3, alphat2, alphaz and alphaq) were detected in both alpha- and beta-cells. In conclusion, our findings demonstrate a clear difference in the localization of G protein alpha-subunits between alpha- and beta-cells, suggesting the involvement of specific receptor transduction pathways for the neuronal/hormonal regulation of alpha- and beta-cell functions.