REGENERATION OF BETA-CELLS IN RESPONSE TO ISLET INFLAMMATION

Subtotal pancreatectomy (90%) in Lewis rats induces chronic islet infl ammation and tissue damage in the remaining pancreas 4 months after su rgery. Concomitantly, significant enlargement of the islets of Langerh ans was observed (90% pancreatectomy: islet/pancreas area: 25.6 +/- 9. 6 x 10(-3), beta-cell/pancreas area: 12.4 +/- 4.4 x 10(-3); n = 4; con trols without pancreatectomy: islet/pancreas area: 5.5 +/- 1.7 x 10(-3 ), beta-cell/pancreas area: 4.6 +/- 1.5 x 10(-3); n = 4; p < 0.05, res pectively). Islet growth is mainly due to an increase in beta-cell mas s. Beta-cell regeneration was not caused by the surgical manipulations or by metabolic stress. The former was ruled out by performing 10% pa ncreatectomy which did not cause islet enlargement after 4 months (isl et/pancreas area: 13.6 +/- 11.3 x 10(-3), beta-cell/pancreas area: 7.1 +/- 2.0 x 10(-3); n = 3). An influence of metabolic stress was exclud ed by continuous substitution of syngenic islet antigens, which inhibi ts insulitis. In the absence of islet inflammation, despite persistent metabolic stress, beta-cell regeneration did not occur (islet/pancrea s area: 7.0 +/- 5.5 x 10(-3), beta-cell/pancreas area: 5.5 +/- 4.1 x 1 0(-3); n = 4). Continuous treatment of animals after 90% pancreatectom y by insulin implants (1.5 U/day) avoided insulitis and beta-cell grow th (islet/pancreas area: 9.2 +/- 1.1 x 10(-3), beta-cell/pancreas area : 6.8 +/- 1.0 x 10(-3), n = 3): All enlarged islets observed 4 months after 90% pancreatectomy without further treatment were infiltrated. T hus, beta-cell growth appears to be a response to insulitis. The stimu lus for beta-cell growth could result from tissue damage caused by inf iltrating cells or from cytokines secreted by the infiltrating cells, or both.