(A) Mouse and (B) human islets transduced with viruses selectively expressing either TALK-1 WT or TALK-1 Leu114Pro and the NanoLuc-proinsulin luciferase insulin reporter. Islets were monitored for total secreted luciferase following exposure to 5 mM or 14 mM glucose. A radioimmunoassay was run on islets transduced with viruses selectively expressing either TALK-1 WT or TALK-1 Leu114Pro (C) to measure insulin secretion in response to 5 mM and 14 mM glucose as well as (D) total insulin content. Mean ± SEM; n = 6 animals (14 mM glucose, A), n = 3 animals (5 mM glucose, A); n = 8 human donors (14 mM glucose, B), n = 5 human donors (5 mM glucose, B), n = 6 animals (C and D) (t test, *P < 0.05).