Formation of a Human β-Cell Population within Pancreatic Islets Is Set Early in Life

Context: Insulin resistance can be compensated by increased functional pancreatic β-cell mass; otherwise, diabetes ensues. Such compensation depends not only on environmental and genetic factors but also on the baseline β-cell mass from which the expansion originates. Objective: Little is known about assembly of a baseline β-cell mass in humans. Here, we examined formation of β-cell populations relative to other pancreatic islet cell types and associated neurons throughout the normal human lifespan. Design and Methods: Human pancreatic sections derived from normal cadavers aged 24 wk premature to 72 yr were examined by immunofluorescence. Insulin, glucagon, and somatostatin were used as markers for β-, α-, and δ-cells, respectively. Cytokeratin-19 marked ductal cells, Ki67 cell proliferation, and Tuj1 (neuronal class III β-tubulin) marked neurons. Results: Most β-cell neogenesis was observed preterm with a burst of β-cell proliferation peaking within the first 2 yr of life. Thereafter, little indication o...