The nontumoral endocrine pancreas was studied immunocytochemically and ultrastructurally in 12 patients with isolated insulinomas. Changes affecting hormone content and secretion of B-, A-, and D-cells were found in the islets of insulinoma-bearing patients when compared with controls, in terms of a significant decrease of the insulin-immunoreactive tissue areas and an increase in the glucagon- and somatostatin-immunoreactive ones. Conversely, only in two of the patients examined were PP-immunoreactive tissue areas augmented. Diffuse ducto-endocrine proliferation (nesidioblastosis) was also a common feature in the tumor-associated pancreas. Both morphometry and qualitative features revealed that islet cell hyperplasia occurs in the presence of insulinoma. Ultrastructural examination revealed that the functional activity of B-cells is substantially depressed in the insulinoma-bearing patients, whereas it is maintained or even enhanced in the other cell types. The islet content in immunoreactive insulin decreases along with duration of hypoglycemic symptoms. The present findings indicate that, in the presence of an insulinoma, the endocrine pancreas undergoes changes that can be regarded as an adaptive response to the chronic excess of insulin and are possibly responsible for the patients’ postoperative clinical cours
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