Tris (Hydroxymethyl) Aminomethane (THAM) Induced Stimulation of Insulin Release by Islets of Langerhans Previously Isolated from Rat Pancreas

Islets isolated from rat pancreas were studied in regard to release of immunoreactive insulin (IRI) as influenced by changes in glucose concentration and pH and type of buffer in the incubation media. The pH of the media was varied from 7.4 to 9.0. For phosphate and bicarbonate buffered media, change in pH did not result in significant change in IRI release rates. For media containing the pH buffer and chelating compound THAM (Tris [hydroxymethyl] aminomethane), IRI release increased significantly with increase in either THAM concentration or pH. Since increase in pH results in increase in that fraction of THAM which is in the unionized, therefore presumably more readily penetrating form, it is postulated that THAM molecules penetrate and act at intracellular loci to induce insulin release, possibly by chelating Zn complexed with insulin in beta cell granules.