Cysteamine exerts multiple effects on the endocrine cells of the rat pancreas

We have studied the effects by cysteamine in vitro and in vivo on hormone production and islet cell metabolism in isolated pancreatic islets and perfused pancreas of the rat. In isolated islets, cysteamine dose-dependently depleted somatostatin immunoreactivity by 50% after 60 min exposure to 1 mmol/l of the compound. This effect appeared to be independent of interaction of the drug with secretion of somatostatin from the pancreatic D-cells. Cysteamine, however, interacted acutely not only with the D-cells, but also markedly suppressed glucose-induced insulin release. Moreover, cysteamine inhibited islet glucose oxidation, an effect which reflects interference with the metabolism mainly of the B-cells. The effect of cysteamine on glucose-induced insulin release was prolonged, since it was still observed in the isolated rat pancreas perfused 24 h after in vivo treatment with cysteamine. In contrast to the effects on glucose-induced insulin release, the response to glibenclamide remained unaffected by a previous exposure to cysteamine in vivo. However, both glucose- and glibenclamide-induced somatostatin secretion was reduced by 50%, whereas basal glucagon secretion was significantly enhanced in pancreata from cysteamine-treated rats vs. control rats. We conclude that (1) cysteamine does not specifically affect the D-cells of the islets, and (2) the multiple effects by cysteamine on islet cell function, particularly on B-cell metabolism and secretion, renders the compound unsuitable for the study of paracrine interactions in the islets.