Intranuclear Rodlets in Human Pancreatic Islet Cells

Abstract

Intranuclear rodlets (INRs) are rod-shaped intranuclear inclusions that we have described in neurons of the human brain. We recently identified these structures in pancreatic islet cells. The objectives of this study are to describe the light microscopic features and cellular pattern of distribution of INRs in human pancreatic islet cells. Double immunofluorescence staining was performed on 5 human pancreatic tissue samples for the detection of class III beta tubulin (C3T) to detect INRs and for promyelocytic leukemia (PML) protein to examine the relationship between PML and INRs. Intranuclear rodlets were detected in 22.99% of pancreatic B cells compared with only 3.11%, 1.80%, and 1.60% of A, D, and PP cells, respectively. Twenty-four percent of C3T-immunoreactive INRs showed partial or complete immunoreactivity for PML. Promyelocytic leukemia staining within the nuclei of B cells was confined to INRs and was not present in the typical PML bodies present in other cell types. Spatially, PML and C3T staining of islet cell INRs appeared to be mutually exclusive within individual INRs. Intranuclear rodlets are present within the nuclei of pancreatic islet cells, where they reside predominantly but not exclusively in B cells. Immunoreactivity of B-cell INRs for PML suggests that the functional significance of INRs may be related to that of PML and/or PML bodies. Conversely, the exclusive localization of PML staining to INRs in B cells indicates that PML's function in B cells is selectively associated with INRs. The mutually exclusive pattern of PML and C3T staining suggests dynamic interactions between these 2 proteins in B-cell INRs. In light of evidence for the involvement of INRs and of PML bodies in disease, it will be of interest to investigate these structures in animal models of diabetes and in human diabetes.