2090-LB: Characters of Intra-islet Ductal Cells Related to Alpha-Cell Regeneration in Zinc-Binding Site–Mutated CRY1-Expressing Diabetic Mice

Introduction & Objective: We previously suggested that the regions of intra-islet ductal cells (IIDCs) play roles as the source for endocrine cells, particularly for α-cells, in C414A-CRY1 transgenic mice (TG) (ADA 2023), the characters of IIDCs relevant to the α-cell neogenesis are yet unknown. To clarify the points, we conducted experiments in terms of reactivity to DBA-lectin as well as of the expression of TFF2.

Methods: The cells constituting developed IIDC (of duct periphery longer than 500 µm) in TG were classified as strongly or weakly positive both for anti-TFF2 antibodies and for DBA-lectin. The positional correlation among glucagon-producing cells present in IIDC compartments and the classified IIDC were examined.

Results: Immature IIDCs embedded inside islets were homogeneous for DBA-lectin-reactivity as reported previously: DBA-lectin-weakly positive (ADA 2019). By contrast, it was newly uncovered that developed IIDCs showed variations in phenotypes for the reactivities to DBA-lectin. Heterogeneity in TFF2 expression was also observed in developed IIDCs. Glucagon-producing cells were more frequently located near DBA-lectin-weakly positive IIDCs (~54% higher than near DBA-lectin-strongly positive ones; P<0.01, t-test). While glucagon-producing cells were more frequently located near TFF2-strongly expressing IIDCs (~42% higher than near TFF2-weakly expressing ones; P<0.001, t-test). Furthermore, DBA-lectin-strongly positive IIDCs tended to be TFF2-weakly expressing ones.

Conclusion: Our results suggest that TFF2 in IIDCs promotes α-cell neogenesis and/or plays some important roles in the maintenance of newborn α-cells. DBA-lectin-strongly positive characteristics of IIDCs possibly suppress TFF2 expression, thereby acting inhibitory manner for α-cell neogenesis in such IIDCs.