Biochemical and morphological investigations of 30 human insulinomas

Thirty human insulinomas have been investigated histologically and their immunoreactive insulin (IRI) content estimated. In most cases immunohistological and ultrastructural studies were also performed and the percentage of proinsulin-like components (PLC) in the tumour determined. Except for 1 case the IRI concentration in the tumours was lower (0.01–89.0 U/g) than in the islet tissue. Histologically, immunohistologically and ultrastructurally a variable number of tumour cells contained few and often no beta-granules, indicating a decreased storage capacity for insulin. This defective storage capacity seems to be the major functional abnormality of insulinoma cells. Ultrastructurally four types of insulinoma can be distinguished. The ultra-structural diagnosis of an insulinoma can only be made in type I (typical beta-granules, 13 cases) and type II (typical and atypical granules, 7 cases) but not in type III (atypical granules only, 4 cases) and type IV (virtually agranular, 4 cases). The type IV tumours had the lowest IRI concentration and did not respond to diazoxide treatment. The IRI concentration of the uninvolved pancreas of 19 patients was 2.0±0.2 U/g and in the range of non-diabetic adults. — The percentage PLC in 19 insulinomas was higher (5.3–22%) than in the pancreas of human adults with and without insulinoma (1.7–4.8%). The percentage of PLC in the serum of patients with insulinoma was always higher than in their tumours (33–61%). It is suggested that the higher PLC levels found in the tumour and serum of insulinoma patients are the consequence of the reduced storage capacity of the tumour cells resulting in a rapid passage through the granular route or even a non-granular release of newly synthesized insulin.