Impaired Insulin Processing in Human Insulinoma

Abstract

Disorders of pancreatic beta cell function cause different clinically important diseases. Among the pancreatic endocrine tumours, functioning insulinomas give raise to persistent hyperinsulinemic hypoglycemia. This is due to inappropriate proinsulin-insulin conversion and faulty insulin secretion. However, like normal beta cells, functioning insulinomas form and store secretory granules which contain insulin and this is shown in panel A. The cytoplasm of this tumour cell contains numerous dense core secretory granules which are all positive for insulin as detected by immunogold electron microscopy. Despite this, the insulin-containing secretory granules differ ultrastructurally from those in normal human beta cells (cf. Fig. 44). Most of them have no halo and crystalloid cores are only occassionally detectable. Therefore, the secretory granules resemble immature secretory granules of normal beta cells. Patients with functioning insulinomas have not only high plasma insulin levels but also high plasma proinsulin levels.