The transgenic mice ubiquitously expressing the zinc-binding site-mutant CRY1 (C414A-CRY1) show early onset diabetes mellitus similar to human MODY characterized by β-cell dysfunction. In the Tg mice with age, atypical ductal structures emerged inside islets, suggesting that islet cells can transdifferentiate to duct-like cells as we have reported at ADA Scientific Sessions in 2017 and 2018. To explore further molecular features of intra-islets ducts, we conducted staining experiments for Dolichos biflorus agglutinin (DBA) lectin in the pancreatic sections of well-matured mice. The results showed that high levels of staining for DBA lectin were observed in normal ducts of both wild type and Tg mice. In contrast, majority of intra-islet ductal structures especially still not fully developed small ones were weakly positive for DBA lectin, suggesting immaturity for ductal functions of the intra-islet ductal cells. Furthermore, the variation of the staining levels for DBA lectin in intra-islet ductal cells was evidently larger than that in other ductal cells, indicating heterogeneity in the cell functions among intra-islet ductal cells. We also found that remarkably high accumulation of FAM98A, an RNA-binding protein whose functions are still not decisive, was observed in the intra-islet ducts in the Tg mice. In normal ducts, moderate staining of FAM98A was observed. As for pancreatic endocrine cells, although as a whole the immunostaining levels were much weaker than those of acini and ductal cells, discernable staining of FAM98A is detected in both α and β cells of islets. Taken together, our results indicate that intra-islet ductal cells have unique feature distinct from normal ductal cells, and suggest that FAM98A may play important roles in the generation of atypical ductal cells from non-ductal cells in the islet.

Disclosure

S. Okano: None. A. Yasui: None. S. Kanno: None. K. Satoh: None. M. Igarashi: None. O. Nakajima: None.

Funding

Japan Society for the Promotion of Science; Tohoku University

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.