β-cell Replication Is The Primary Mechanism Subserving The Postnatal Expansion Of β-cell Mass In Humans

摘要

OBJECTIVE-Little is known about the capacity, mechanisms, or timing of growth in β-cell mass in humans. We sought to establish if the predominant expansion of β-cell mass in humans occurs in early childhood and if, as in rodents, this coincides with relatively abundant β-cell replication. We also sought to establish if there is a secondary growth in β-cell mass coincident with the accelerated somatic growth in adolescence.rnRESEARCH DESIGN AND METHODS-To address these questions, pancreas volume was determined from abdominal computer tomographies in 135 children aged 4 weeks to 20 years, and morphometric analyses were performed in human pancreatic tissue obtained at autopsy from 46 children aged 2 weeks to 21 years.rnRESULTS-We report that i) β-cell mass expands by several-fold from birth to adulthood, 2) islets grow in size rather than in number during this transition, 3) the relative rate of β-cell growth is highest in infancy and gradually declines thereafter to adulthood with no secondary accelerated growth phase during adolescence, 4) β-cell mass (and presumably growth) is highly variable between individuals, and 5) a high rate of β-cell replication is coincident with the major postnatal expansion of β-cell mass.rnCONCLUSIONS-These data imply that regulation of β-cell replication during infancy plays a major role in β-cell mass in adult humans.