Abstract:
: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.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Saï P,Boillot D,Boitard C,Debray-Sachs M,Reach G,Assan Rdoi
10.1007/BF00282521subject
Has Abstractpub_date
1983-11-01 00:00:00pages
418-23issue
5eissn
0012-186Xissn
1432-0428journal_volume
25pub_type
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