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Apoptosis Participates in the Remodeling of the Endocrine Pancreas in the Neonatal Rat¹

EP Joslin Research Laboratories (L.S., C.J.C., S.B.-W.), Joslin Diabetes Center and the Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02215; and Departments of Medicine and Physiology (D.T.F.), University of Alberta, Edmonton, Canada T6G 2H7

Address all correspondence and requests for reprints to: Dr. Susan Bonner-Weir, Joslin Diabetes Center, 1 Joslin Place, Boston, Massachusetts 02215. E-mail: bonners{at}joslab.harvard.edu

In rodents, shortly after birth a lack of increase in pancreatic weight and in islet mass have been reported during a time of overall body weight increase. To understand this regulation of the neonatal growth of the ß cell mass, we studied Sprague Dawley rats at 2, 9, 13, 17, 20, 24, and 31 days of age for ß cell replication, ß cell mass, and cell size and for the presence of ß cell apoptosis. ß cell mass was stable from 2–20 days (range: 0.91 ± 0.2 to 1.33 ± 0.23 mg) and increased thereafter. ß cell replication progressively decreased. Condensed apoptotic nuclei were identified and counted on paraffin sections using the fluorescent dye propidium iodide. Apoptotic ß cell nuclei were found at a basal rate (1.54 ± 0.22%) at 2, 9, and again after 20 days of age. However, at 13 and 17 days, the incidence of apoptosis was significantly increased (3.64 ± 0.45%). The decreased replication and the increased incidence of apoptosis in the ß cells strongly suggest a wave of neogenesis of ß cells to maintain the constant ß cell mass. These data show that the endocrine pancreas undergoes significant modification during neonatal life and that apoptosis is an important mechanism in this remodeling of the ß cell mass. Whether a selective deletion of some population of ß cells occurs is unclear, but a dysregulation of this remodeling process could have important effects on the pancreatic ß cell mass.

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