Discordance of Exocrine and Endocrine Growth After 90% Pancreatectomy in Rats

Abstract

As we have previously shown, by 8 wk after 90% pancreatectomy (PX) in the rat, there is considerable regeneration of both exocrine and endocrine pancreas. In this study we examine the growth of both the exocrine and endocrine tissue 3, 7, 14, and 21 days after PX by following the pancreatic content of insulin, glucagon, and amylase as well as the mitotic indices for exocrine and islet β-cells. By 7 days the pancreatic remnant weighed more than the anatomically equivalent tissue in the sham, the remnant equivalent. The growth of the exocrine tissue and the endocrine β-cells was discordant during these initial weeks after PX, as shown by the mitotic index. The mitotic index, measured as accumulated mitotic figures after a 4-h colchicine treatment, for both the exocrine and β-cells in the sham animals was low and unchanging at the different time points (∼0.5%). At 3 and 7 days after PX, both the exocrine and β-cells had mitotic indices three- to fourfold that of the sham animals. At 14 days after PX, the exocrine cells had a slightly, albeit significantly, elevated mitotic index, whereas that of the β-cells was still double that of the shams. By 21 days there was no difference in mitotic index for exocrine tissue, but the β-cells on the PX animals had a mitotic index still double that of the shams. Another index of growth, the cell birthrate, was estimated at 7 days from the slope of regression lines of the mitotic frequency accumulated 1, 2, 3, and 4 h after colchicine. The cell birthrates of both the exocrine cells (PX 3.8 ± 0.96%, sham 0.96 ± 0.72%) and the β-cells (PX 7.2 ± 1.7%, sham 0.72 ± 0.96%) were significantly elevated in the pancreatic remnant. Thus, both exocrine cells and endocrine β-cells undergo considerable growth in the initial 3 wk after PX. However, there is discordance in their growth with respect to each other. In addition, these adult β-cells have a greater and more sustained growth than previously thought possible. The PX model could therefore become a useful model for studying the mechanisms of both exocrine and endocrine regeneration.