Compensatory Growth of Pancreatic β-Cells in Adult Rats After Short-Term Glucose Infusion

  1. Gordon C Weir
  1. Elliot P. Joslin Research Laboratories of the Joslin Diabetes Center, New England Deaconess Hospital Brigham Women's Hospital, Harvard Medical School Boston, Massachusetts
  1. Address correspondence and reprint requests to Dr. S. Bonner-Weir, E.P. Joslin Research Laboratories, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215.

Abstract

The extent to which adult pancreatic β-cells can respond in vivo to a sustained glucose stimulus by increasing their mass through either hyperplasia or hypertrophy has remained unanswered. Therefore, we studied the in vivo effect of short-term (96-h) hyperglycemia on the growth of β-cells by infusing adult rats with 35 or 50% glucose or 0.45% saline. After 96 h of glucose infusion, the β-cell mass, quantified by point-counting morphometrics of immunoperoxidase-stained paraffin sections, showed a 50% increase (9.57 ± 0.87 mg, n = 5, 50% glucose infused; 9.50 ± 1.23, n = 7, 35% glucose infused; 6.15 ± 0.55, n = 6, 0.45% saline infused). This growth was selective for β-cells; the non-β-cell mass was unchanged. The mitotic index, measured by accumulated mitotic frequency after a 4-h colchicine treatment, increased fivefold in glucose-infused animals compared to saline-infused animals. This enhanced replication of β-cells provides evidence for increase in cell number or hyperplasia. In addition, hypertrophy of the β-cells was also quantified. Mean cell volume, determined from the mean cell cross-sectional area measured planimetrically from low-magnification electron micrographs, increased to 150% of control values after 96 h of 50% glucose infusion. Seven days after the 96-h infusion, in reversal experiments, the β-cell mass had not returned to saline-infused levels. In addition, the non-β-cell mass of glucose-infused animals had increased. The mitotic index of the β-cells of glucose-infused rats was, however, significantly lower than that of the saline controls, but the mean cell volume of the β-cells remained elevated. Thus, with a short-term in vivo stimulus, adultβ-cells have a far greater capacity to respond with compensatory growth by hyperplasia and hypertrophy than has been appreciated before. Even 7 days after discontinuation of the stimulus, β-cell mass remains elevated.

  • Received April 25, 1988.
  • Revision received July 6, 1988.
  • Accepted July 6, 1988.
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