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The antiprotozoal drug, pentamidine, has been reported to induce hypoglycaemia associated with inappropriately high plasma insulin concentrations, followed by insulindependent diabetes mellitus. It has been suggested that this drug can be toxic to the islet B cell, inducing early cytolytic release of insulin leading to B cell destruction. In order to test this hypothesis, mouse and rat islets were incubated with pentamidine at concentration range of 5×10 to 5×10 mol/1 and exposure times of 3-48 h. The B cell responses to glucose + theophylline and to arginine were suppressed by pentamidine, while insulin release in non-stimulatory conditions was increased. These effects were dose-dependent, time-dependent and irreversible. They were significant for 5 × 10 mol/1 pentamidine, which is a concentration relevant to therapeutic uses. These effects developed more slowly than the toxic effects of streptozotocin and alloxan at the same molar concentration in vitro. Chromium release and Trypan blue exclusion tests support the hypothesis that pentamidine produces islet cell necrosis. [ABSTRACT FROM AUTHOR]

The insulin response of isolated islet cells to glucose and theophylline in vitro was studied after incubation with lymphocytes. The test was employed to explore cell-mediated immunity in diabetics. A significant inhibition of insulin response to glucose and theophylline as compared to insulin release in a 'basal' medium was found after incubation with blood lymphocytes from 21 out of 23 insulin-dependent diabetics (mean secretion index 18±8 versus 118±8 (SEM) % in control subjects). Most of the patients studied had associated autoimmune diseases: all of these displayed inhibition of insulin release. In six cases, the diabetes had a recent onset with no associated autoimmune disease: four of them displayed the same inhibition. No inhibition was found in the 26 control subjects and in seven non-insulin-dependent diabetics (mean secretion index 134±17 versus 145±23 (SEM) % in four control subjects). Lymphocytes inhibiting islet cell response were not cytotoxic against mouse fibroblasts. Twenty-two insulin-dependent diabetics showed islet cell antibodies to human and/or mouse pancreatic islets.. However, an inhibition of insulin release was found with no detectable islet cell antibodies in one case, and the converse in two cases. Lymphocyte cytotoxicity to islet cells could play a role in the natural history of insulin-dependent diabetes. [ABSTRACT FROM AUTHOR]