Survey of mRNAs encoding zinc transporters and other metal complexing proteins in pancreatic islets of rats from birth to adulthood: similar patternsin the Sprague-Dawley and Wistar BB strains

The zinc content in the pancreatic beta cell is among the highest of the bo dy, but information about which proteins might handle zinc ill the beta cel l is unknown. In the present work RT-PCR was used to obtain clues about the developmental expression of genes encoding metal complexing proteins in th e pancreatic islets of the normal Sprague Dawley rat and the BE diabetes re sistant (BBDR) rat. The BBDR rat possesses beta cells genetically identical to the BB diabetes prone (BBDP) rat which exhibits an autoimmune diabetes quite similar to type 1 diabetes in humans, but in contrast to the BBDP rat , the islets of the BBDR rat are amenable to study because they are not des troyed by immune attack. There was no difference in the expression of any o f the genes studied between the two strains of rats. mRNAs encoding zinc tr ansport proteins ZnT-1 and ZnT-4, as well as calreticulin, ferritin heavy a nd light chains, metallothionein 1, metallothionein 3, Nramp1, Nramp2, tran sferrin, and the transferrin receptor were readily detected in pancreatic i slets of 10-day-old, 5-week-old, and adult (60 to 90-day-old) rats. In cont rast to the islet, mRNAs encoding metallothionein 3, Nramp1, Nramp2, ZnT-2, ZnT-3, and ZnT-4 and transferrin were not detected in the whole pancreas o f adult Sprague - Dawley rats. In the whole pancreas of 3-day-old rats, ZnT -1 was the only zinc transporter mRNA detected and its level was moderate. Moderate to high levels of mRNA encoding calreticulin and the light and hea vy chains of ferritin, as well as transferrin and the transferrin receptor, were detected ill whole pancreas at 3 days. ZnT-2 and ZnT-3 mRNAs were pre sent in low to moderate levels in pancreatic islets of 10-day and 5-week-ol d rats, but were absent in 3-day-old pancreas and islets of adult animals. These results indicate that expression of these proteins is developmentally regulated in the islet. In both Sprague Dawley and BE rats, high levels of mRNAs encoding known beta cell proteins as controls (cytochrome b558, quin one reductase, the tricarboxylic acid transport protein and the receptors f or IGF-1 and IGF-2 and insulin) were present in islets from 10 days to adul thood. Levels of mRNAs encoding quinone reductase, the tricarboxylic acid t ransport protein cytochrome b558 and the receptors for IGF-2 and insulin, w ere low or absent in 3-day-old and adult pancreas. BB rats were studied in an attempt to discern a difference between normal rats and the BE strain of rats, because, perhaps, delayed expression of a beta cell protein results in failure of immune tolerance against the beta cell. According to this par adigm none of the proteins examined in the current study appear to be a can didate for initiating an immune response in the BB rat, (C) 2000 Elsevier S cience Ireland Ltd. All rights reserved.