Fig. 4: Activation of β-cell NKAs is a conserved mechanism for Gi/o-GPCR control of islet Ca2+ handling. | Nature Communications

Fig. 4: Activation of β-cell NKAs is a conserved mechanism for Gi/o-GPCR control of islet Ca2+ handling.

From: Gi/o protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na+/K+ ATPase activation

Fig. 4

A Representative WT islet clonidine (Clon) and ouabain (Oua) [Ca2+]i responses (F/Fmin). B Percentage of WT islets displaying [Ca2+]i oscillations with Clon (orange) and Clon + Oua (blue; n = 3). C WT islet [Ca2+]i plateau fraction before treatment (white), after Clon (orange), and after Clon + Oua (blue; n = 3). D Representative βGi/o-DREADD-expressing WT islet CNO and Oua [Ca2+]i responses. E Percentage of βGi/o-DREADD-expressing islets displaying [Ca2+]i oscillations in response to CNO (pink) and CNO + Oua (blue; n = 3). F βGi/o-DREADD-expressing WT islet [Ca2+]i plateau fraction before treatment (white), after CNO (pink), and after CNO + Oua (blue; n = 3). G Representative WT islet Exendin-3 (9–39) (Ex9) and SST [Ca2+]i responses. H Percentage of WT islets displaying [Ca2+]i oscillations in response to Ex9 (purple) and Ex9 + SST (green; n = 3). (I) WT islet [Ca2+]i plateau fraction before treatment (white), after Ex9 (purple), and after Ex9 + SST (green; n = 3). J Representative WT islet L-054,264 [Ca2+]i responses. K Percentage of WT islets displaying [Ca2+]i oscillations before (white) and after L-054,264 (yellow; n = 3). (L) WT islet [Ca2+]i plateau fraction before (white) and after L-054,264 (yellow; n = 3). M Representative δGi/o-DREADD islet CNO/SST [Ca2+]i responses. N Normalized δGi/o-DREADD islet [Ca2+]i oscillation period before treatment (magenta; n = 7), after CNO (pink; n = 7), and after CNO + SST (green; n = 4). O Normalized δGi/o-DREADD islet [Ca2+]i AUC before treatment (magenta), after CNO (pink), and after CNO + SST (green; n = 4). P Normalized δGi/o-DREADD islet [Ca2+]i plateau fraction before treatment (magenta; n = 6), after CNO (pink; n = 6), and after CNO + SST (green; n = 3). Q δGi/o-DREADD islet insulin secretion without CNO (magenta) and with CNO (pink; 2G: n = 3, 7 G: n = 3, 9 G: n = 6). R SST secretion from δGi/o-DREADD islets without CNO (magenta) and with CNO (pink; 9G: n = 3). S WT islet insulin secretion without CNO (white) and with CNO (pink; 1G: n = 3, 11 G: n = 3). Statistical analysis was conducted using unpaired two-sided two-sample t tests (B, E, H, K, L, R), or one-way ANOVA with Šidák’s post-hoc multiple comparisons tests (C, F, I, N–Q, S); *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. Source data and exact P values are provided as a Source Data file.

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