1. Twenty-nine normal guinea pigs were injected with 10 mg. of cortisol daily for four to five weeks; fifteen animals were used as controls. This treatment inhibited the normal growth of the animals and induced a moderate atrophy of the adrenal glands. At the end of the treatment the glucose tolerance was reduced to a small but significant extent.
2. It was found that cortisol treatment through a persistent small hyperglycemia (average increase of blood glucose was 30 mg. per 100 ml.) or through some other unknown mechanism induced large hyperplasia and hypertrophy of the islets with an increase in proportion of their beta cells. One month after interruption of cortisol treatment with the islet tissue still hyperplastic, blood sugar levels were in the normal range.
3. Ligation of the pancreatic duct produced an almost complete atrophy of the typical exocrine acinar tissue in forty-three guinea pigs. In these animals cortisol treatment raised the blood sugar levels approximately to the same extent as in normal guinea pigs.
4. Pronounced hyperplasia of islets was induced whether the treatment was started immediately after ligation of the pancreatic duct or one month later when the ordinary acinar cells already had disappeared, thus demonstrating that normal acinar tissue is not indispensable for induction of islet hyperplasia.
5. There was some histological evidence that new islet cells may originate from cells in the walls of small pancreatic ducts.