TY - JOUR TI - Pharmacological inhibition of thioredoxin reductase increases insulin secretion and diminishes beta cell viability AU - Brüning, Dennis AU - Hatlapatka, Kathrin AU - Lier-Glaubitz, Verena AU - Andermark, Vincent AU - Scherneck, Stephan AU - Ott, Ingo AU - Rustenbeck, Ingo T2 - Naunyn-Schmiedeberg's Archives of Pharmacology AB - Apparently, both a decrease in beta cell function and in beta cell mass contribute to the progressive worsening of type 2 diabetes. So, it is of particular interest to define factors which are relevant for the regulation of insulin secretion and at the same time for the maintenance of beta cell mass. The NADPH-thioredoxin system has a candidate role for such a dual function. Here, we have characterized the effects of a highly specific inhibitor of thioredoxin reductase, AM12, on the viability and function of insulin-secreting MIN6 cells and isolated NMRI mouse islets. Viability was checked by MTT testing and the fluorescent live-dead assay. Apoptosis was assessed by annexin V assay. Insulin secretion of perifused islets was measured by ELISA. The cytosolic Ca2+ concentration was measured by the Fura technique. Acute exposure of perifused pancreatic islets to 5 μM AM12 was without significant effect on insulin secretion. Islets cultured for 24 h in 0.5 or 5 μM AM12 showed unchanged basal secretion during perifusion, but the response to 30 mM glucose was significantly enhanced by 5 μM. Twenty-four-hour exposure to 5 μM AM12 proved to be without effect on the viability of MIN6 cells, whereas longer exposure was clearly toxic. Islets were more susceptible, showing initial signs of apoptosis after 24-h exposure to 5 μM AM12. The activity of the NADPH-thioredoxin system is indispensable for beta cell viability but may have a limiting effect on glucose-induced insulin secretion. DA - 2021/01/19/ PY - 2021 DO - 10.1007/s00210-020-02046-2 DP - Springer Link J2 - Naunyn-Schmiedeberg's Arch Pharmacol LA - en SN - 1432-1912 UR - https://doi.org/10.1007/s00210-020-02046-2 Y2 - 2021/01/26/17:27:42 ER -