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β-Cell Replication Is the Primary Mechanism Subserving the Postnatal Expansion of β-Cell Mass in Humans

¹ Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, California
² Division of Endocrinology, Diabetes and Hypertension, UCLA David Geffen School of Medicine, Los Angeles, California
³ Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota

Corresponding author: Peter C. Butler, Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, 24-130 Warren Hall, 900 Veteran Ave., Los Angeles, CA 90095-7073. E-mail: pbutler{at}mednet.ucla.edu

Abbreviations: CT, computed tomography

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.

RESEARCH 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.

RESULTS— We report that 1) β-cell mass expands by severalfold 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.

CONCLUSIONS— These data imply that regulation of β-cell replication during infancy plays a major role in β-cell mass in adult humans.

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