Metformin impairs glucose-stimulated [Ca2+]i responses. (a–c) Glucose-stimulated [Ca2+]i responses (Mean +/− SEM) from islets treated for 1 day with 20 μM (a), 200 μM (b), and 1 mM metformin (c). (d–f) Glucose-stimulated [Ca2+]i responses (Mean +/− SEM) in islets treated for 2 days with 20 μM (d), 200 μM (e), and 1 mM metformin (f). (g–i) Glucose-stimulated [Ca2+]i responses (Mean +/− SEM) in islets treated for 3 days with 20 μM (g), 200 μM (h), and 1 mM metformin (i). A total of 436 individual islet traces were studied in two trials combined for analysis; 17–33 islets were recorded for each metformin condition. Phases of the calcium response are labeled only in (a) but occur similarly for each panel. Statistically different means in [Ca2+]i between untreated and metformin-treated islets are reported as follows: N.S. = not significant, #P < 0.10, ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001.