Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats

• DOI: 10.1073/pnas.0500178102
• Publication Date: 2005-02-15T01:24:30Z
• Authors: Tammara Watts; Irene Berti; Anna Sapone; Tania Gerarduzzi; Tarcisio Not; Ronald Zielke; Alessio Fasano
• Keywords: Intestinal Permeability; Pathogenesis

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased plays role pathogenesis T1D. In BB diabetic-prone rat model T1D, intraluminal zonulin levels were elevated 35-fold compared control diabetic-resistant rats. Zonulin up-regulation coincident with decreased small transepithelial electrical resistance, followed by production autoantibodies against pancreatic beta cells, which preceded onset clinically evident T1D ≈25 days. those rats did not progress diabetes, both resistance similar detected controls. Blockade receptor reduced cumulative incidence 70%, despite persistence up-regulation. Moreover, treatment responders seroconvert islet cell antibodies. Combined together, these findings suggest zonulin-induced loss barrier function is involved model.