Tolbutamide-induced changes of the DNA, protein and insulin content and the secretory activity of isolated rat pancreatic islets.

ABSTRACT

Following prolonged administration of tolbutamide the DNA- and protein content per islet was enhanced but the IRI content per islet was diminished. Glucose-induced (2.0, 8.0 or 16.6 mM) and leucine-induced (12.5 or 25.0 mM) IRI release from isolated islets, as well as 14C02-production from U-14C glucose, were decreased. Theophylline (5.0 mM) restored the glucose sensitivity of the islets towards normal. The results indicate that tolbutamide-induced islet cell hyperplasia does not entail islet hyperfunction, as previously thought. Decreased IRI release may partially be explained by a tolbutamide-induced alteration of the adenylate cyclase/phosphodiesterase system of the B-cell.