Pentamidine, a new diabetogenic drug in laboratory rodents.
The antiprotozoal drug, pentamidine, has been reported to induce hypoglycaemia associated with inappropriately high plasma insulin concentrations, followed by insulin-dependent 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 x 10(-11) to 5 x 10(-3) mol/l 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 x 10(-7) mol/l 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. 51Chromium release and Trypan blue exclusion tests support the hypothesis that pentamidine produces islet cell necrosis.
D000578:Amidines / Q000633:toxicity*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D010419:Pentamidine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000578:Amidines; D007328:Insulin; D010419:Pentamidine