Fig. 7: Gi/o-GPCR-mediated β-cell NKA activity depends on tyrosine kinase signaling.

A Representative WT islet SST and dasatinib (Dasa) [Ca2+]i responses (F/Fmin). Insets indicate the percentage of islets exhibiting each type of Dasa [Ca2+]i response. B Percentage of WT islets displaying [Ca2+]i oscillations in response to SST (green) and SST + Dasa (purple; n = 3). C WT islet [Ca2+]i plateau fraction after SST (green) and after SST + Dasa (purple; n = 3). D Relative size of WT islets displaying total (black) or partial (gray) Dasa-mediated inhibition of SST-induced [Ca2+]i oscillations (n = 3). E Representative WT islet SST and NSC 87877 (NSC) [Ca2+]i responses. Insets indicate the percentage of islets exhibiting each type of NSC [Ca2+]i response. F Percentage of WT islets displaying [Ca2+]i oscillations in response to SST (green) and SST + NSC (pink; n = 3). G WT islet [Ca2+]i plateau fraction after SST (green) and after SST + NSC (pink; n = 3). H Relative size of WT islets displaying total (black) or partial (gray) NSC-mediated inhibition of SST-induced [Ca2+]i oscillations (n = 3). I Representative WT islet insulin (Ins) and Dasa [Ca2+]i responses. J Percentage of WT islets displaying [Ca2+]i oscillations in response to Ins (red) and Ins + Dasa (purple; n = 3). K WT islet [Ca2+]i plateau fraction before treatment (white), after Ins (red), and after Ins + Dasa (purple; n = 3). L Representative immunoblots (IBs) of WT islet cell lysates that were treated for 15 min with vehicle (H2O), SST, or Ins at 25 °C. IBs were probed for total NKA (ATP1A1; left) and NKA phosphorylated at Y10 (p-ATP1A1Y10; right). p-ATP1A1Y10 bands were normalized to corresponding ATP1A1 bands; normalized p-ATP1A1Y10 bands from SST-/Ins-treated islets were then normalized to p-ATP1A1Y10 bands from vehicle-treated islets. M Average vehicle-normalized islet p-ATP1A1Y10 relative to total ATP1A1 (n = 4). Statistical analysis was conducted using unpaired two-sided two-sample t tests (B–D, F–H, J) or one-way ANOVA with Šidák’s post-hoc multiple comparisons tests (K, M); *P < 0.05, **P < 0.01, and ***P < 0.001. Source data and exact P values are provided as a Source Data file.