A specially developed clamping procedure permitted the easy, complication-free removal of splenic pancreas from rats. Using this biopsy procedure pancreatic tissue was removed from 50- to 90-day-old BB rats to study in a retrospective experimental design the time at which insulitis appears in BB rats, which develop acute, overt diabetes before the age of 120 days. Islets in biopsies taken 18–53 days before the onset of diabetes showed normal structure and were free from any mononuclear infiltrations. Biopsies removed between 2 and 9 days before onset of diabetes in contrast showed widespread insulitis. In five rats in which the biopsy preceded the manifestation of diabetes by 11–16 days, only a small number of pancreatic islets showed small focal mononuclear cell infiltrations. Most of the islets in these five rats had a normal histologic appearance.

Thus the lesions within the islets develop rapidly starting about 2–3 wk before overt diabetes. As revealed by autoradiography, pancreatic beta-cells still surviving at the time of onset of diabetes show a modest increase in replicative activity. Replicative activity of mononuclear inflammatory cells also was observed, suggesting that their accumulation within the islet tissue may result in part from local replication.

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