Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion

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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.