Attenuation of glucose-, ex-4–, and GIP-induced increases in NSCC current in β-cells from TRPM2-KO mice. Attenuation of glucose-, ex-4–, and GIP-induced increases in NSCC current in β-cells from TRPM2-KO mice. A: Ex-4 (10−10 mol/L), 16.6 mmol/L glucose, GIP (10−10 mol/), and 8-pCPT (10 μmol/L) elicited NSCC current increase in wild-type (Wt) β-cells. B: NSCC current increases by the compounds described above were not observed in TRPM2-KO mice. C: NSCC current was maximally activated by 10 μmol/L 8-pCPT-AM at 2.8 mmol/L glucose to a degree similar to that evoked by 16.6 mmol/L glucose, and 10 μmol/L ESI-09 attenuated the current increase with high glucose. Membrane potential was held at −70 mV, and tolbutamide at 100 μmol/L was continuously present when the current was compared between control and tested compounds in A–C. D: High glucose concentration (16.6 mmol/L) compared with 2.8 mmol/L glucose induces more depolarization despite the presence of the same concentration of tolbutamide (tolb) (100 μmol/L). Nitrendipine at 10 μmol/L was added to suppress the voltage-dependent Ca2+ channels for stable recording of resting membrane potential without induction of electrical firing. *P < 0.05 by unpaired test. Number of experiments was six to nine. In C and D, experiments were performed in rat β-cells. Masashi Yosida et al. Diabetes 2014;63:3394-3403 ©2014 by American Diabetes Association