Are 5-hydroxytryptamine-preloaded beta-cells an appropriate physiologic model system for establishing that insulin stimulates insulin secretion?

The release and oxidation of 5-hydroxytryptamine from 5-hydroxytryptamine-p reloaded beta -cells has been used as a surrogate marker for insulin secret ion. Findings made using this methodology have been used to support the con cept that insulin stimulates its own release. In the present studies, the e ffects of 5-hydroxytryptamine on stimulated insulin secretion from isolated perifused rat islets was determined. When added together with stimulatory glucose, 5-hydroxytryptamine (0.5 mM) significantly reduced both phases of 8 mm glucose-induced secretion and reduced the first phase of 15 mM glucose -induced release by 60%, without any effect on sustained insulin release ra tes. Preloading of beta -cells with 0.5 mm 5-hydroxytryptamine for 3 h resu lted in a more severe impairment of 15 mm glucose-induced secretion. First and second phase release rates were reduced by 70 and 55%, respectively. In addition, this pretreatment protocol also abolished 200 muM tolbutamide-in duced insulin secretion from perifused islets. These findings confirm that 5-hydroxytryptamine is a powerful inhibitor of stimulated insulin secretion . The responses of 5-hydroxytryptamine-preloaded beta -cells may not accura tely reflect the biochemical events occurring during the physiologic regula tion of insulin secretion. The suggestion that insulin stimulates its own s ecretion based exclusively on amperometric measurements should be reconside red.