Depletion of Beta Cell Intranuclear Rodlets in Human Type II Diabetes

Intranuclear rodlets (INRs) are rod-shaped intranuclear bodies of unknown function present in the nuclei of pancreatic beta cells. Previous studies have demonstrated a significant depletion of INRs from beta cells in mouse models of type II diabetes, suggesting that they may have pathological significance. The objective of the present study was to determine whether beta cell INRs show quantitative alterations in human type II diabetes. In sections of non-neoplastic pancreas from 23 diabetic patients and 23 controls who had undergone complete or partial pancreatectomy, we detected a significant reduction in the proportion of INRs in insulin-immunoreactive beta cells. In addition, we showed that beta cell INRs are immunoreactive for the RNA-binding protein HuR. The results of this study confirm and extend our previous study and implicate this enigmatic nuclear structure in the cellular pathophysiological mechanisms underlying the development of type II diabetes in humans.