Excessive growth of cultured beta cells from an adult patient with beta cell hyperplasia.

We have studied a 25-year-old female with frequent, severe hypoglycemic episodes. Concurrent with low serum glucose levels, the concentrations of C-peptide and insulin were markedly elevated. Tests for sulfonylurea hypoglycemic agents were negative. Special tests did not disclose any neoplasm. Biopsy of the pancreatic tail revealed islet cell hyperplasia and adenomatosis. About two-thirds of the pancreas was resected, resulting in correction of all metabolic abnormalities. Specific fluorescein-labeled anti-insulin antibodies revealed staining in 60-80% of the cultured cells isolated from the patient's pancreas, while electron microscopy disclosed insulin storage granules in about 80%. By comparison, for each of these findings, the range for cells from normal pancreases was 30-50%. In contrast to these control cells, cells from the patient grew about 2 and 2.6 times more rapidly during the first two cell cycles, and the growth persisted through four cycles. The greater and more enduring growth of the patient's cells in culture must have been at least partly independent of circulating factors. Paracrine/autocrine principles from the beta cells or other islet cells may have been responsible.