122-OR: Insulin and C-Peptide in Human Choroid Plexus of Type 1 Diabetes Mellitus

Abstract

The choroid plexus (CP) produces cerebrospinal fluid (CSF) and forms a blood-CSF barrier. We already reported that mouse CP epithelial (CPE) cells synthesize and secrete insulin in response to serotonin but not glucose. We now report that insulin expression is present in human postmortem CP samples of humans - nondiabetic, T2DM, and T1DM - by RT-qPCR, in situ hybridization and LC-MS/MS based Selected Reaction Monitoring assay. Human CPE contains all the INS splicing machinery and the major INS splicing variants that are present in islets. Known β-cell specific transcription factors are also expressed in CPE, except for PDX1 and PAX4, which are absent. The SRM assay detected INS A-chain, B-chain, and C-peptide at similar levels in nondiabetic, T2DM, and T1DM islets and CP postmortem samples. Islet amyloid polypeptide (IAPP) expression was not detected in CPE in contrast to human islets where INS and IAPP mRNA, as expected, colocalize in β-cells. Furthermore, INS colocalizes with transthyretin (TTR) mRNA in CPE cells but in islets, TTR is expressed in α-cells and not β-cells. We found less or no expression of T1DM autoantigens in CPE compared to β-cells, with the exception of ICA1 (islet cell autoantigen1), which has similar expression in both tissues. In conclusion, human CPE expresses and synthesizes insulin, it is protected from autoimmune destruction and from IAPP amyloidogenic fibril formation. Disclosure Q. Liu: None. M. Zhu: None. C. Mazucanti: None. S. Marenco: None. J. M. Egan: None. Funding National Institute on Aging