Development and growth of islet endocrine cell volume are assumed to mainly depend on cell proliferation. In addition, the partial contribution of islet neogenesis and chromogranin A positive hormone negative cell (CPHN cell) is recently clarified. Detailed evaluation for the islet cell development and growth, however, is not well explored linking to the change of cell replication, neognesis and CPHN cell for each type of endocrine cells in human specimens. For this purpose, we recruited human autopsied pancreata, aged from 24 weeks old to 19 years old (n=32). Formalin-fixed paraffin embedded sections from pancreatic body were used for immunohistochemistry (IHC) and immunofluorescence (IF) analysis. The subjects were divided into 4 groups, Fetus (F: 24-31 weeks), Infant (I : 0-1 years), Child (C : 2-12 years) and Adolescence (A : 13-19 years). Quintuple-IHC with antibodies for glucagon, insulin, somatostatin, pp and Ki-67 was performed for the measurement of islet cell volume density (V) and replication status. Vαand Vβwere increased with age. Vβin A was more abundant than in F (p<0.01). On the other hand, Vδnegatively correlated with age (r=-0.701, p<0.01) and was more in F than in C and A (p<0.01). Ki-67 positive index for αand δ cells showed the highest in F (p<0.01), whereas that of β cells was the highest in I (p<0.01). Neogenic islet density, evaluated in IHC with an antibody for chromogranin A, showed negative correlation with age (r=-0.608, p<0.01). Double-IF with a cocktail of four kinds of antibodies for islet hormones and for chromogranin A was performed to evaluate VCPHN. CPHN cell was identified in both islets and neogenic islets. VCPHNwas more abundant in neogenic islets of F and I than those of C and A. Our results suggest that each kind of islet cell owns a unique pattern of the cell development and growth. In particular, neogenic islet and CPHN cell may play a role as the source of βcells in the later life.
S. Osonoi: None. H. Mizukami: None. K. Takahashi: None. K. Kudo: None. S. Yagihashi: None.