Depletion of Pancreatic Intranuclear Rodlets in Patients with Type 2 Diabetes
Soufiane El Hallani, Pavel Milman, Mei Zhang, John Woulfe. Ottawa Hospital, Ottawa, ON, Canada
Background: Intranuclear rodlets (INRs) are rod-shaped intranuclear inclusions present in neurons of the human brain. We have demonstrated that neuronal INRs are markedly depleted in the Alzheimer Disease and current investigations are exploring the role of INRs in the pathogenesis of neurodegeneration. We also identified these structures in B cells of the pancreatic islets and recently demonstrated the depletion of pancreatic INRs in the mouse models of type 2 diabetes. The objective of this study is to compare the frequency of pancreatic B cells INRs in diabetic and control patients.
Design: Formalin-fixed, paraffin-embedded blocks of normal human pancreas from twelve patients who underwent Whipple procedure were selected as follows: seven cases from confirmed type 2 diabetes patients and five cases from non-diabetic patients as controls. Double immunofluorescence staining was performed on 5um pancreatic tissue sections with anti-class III A tubulin (C3T) to detect INRs, and anti-insulin to detect the pancreatic B cells. Fluorescent images of pancreatic islets (10 per each section) were acquired and manual counts of B cell nuclei and INRs containing nuclei were performed.
Results: As represented in Figure 1A, the proportion of B cell containing INRs was significantly reduced in diabetic patients (median 6.8%; SD 2.6; range [3.6% – 9.8%]) compared with control patients (median 21.5%; SD 2.5; range [20.2% – 25.1%]); scal bar at 20um. The box plot diagram (Figure 1B) shows the differential of INRs frequency in diabetes and control groups (p<0.0001).
Conclusions: The results of the present study represent the first report of INRs depletion in human pancreatic B cells of type 2 diabetes patients. In light of the considerable evidence for B cell dysfunction in the pathogenesis of type 2 diabetes, it will be of interest to investigate the role of INR depletion in the “functional degeneration” of pancreatic B cells.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 214, Tuesday Morning