Figure 5. Islet proteins show correlation architecture to specific Ca²⁺ parameters.

(A) Unsupervised clustering of correlation coefficients between protein abundance Z-scores and Z-scores for the Ca²⁺ parameters indicated. Islet proteins show differential correlation values to basal Ca²⁺, excitatory Ca²⁺ (detrended average values for 8G, 8/QLA, and 8/QLA/GIP), active duration and pulse duration in 8G (8G P_D and A_D), and silent durations (S_D) in 8G, 8G/QLA, and 8G/QLA/GIP. Correlation coefficients for other parameters are indicated in Figure 5—figure supplement 1. (B) Histograms representing the number of proteins that are correlated (red) and anticorrelated (blue) to 8G A_D. ENCODE & CHEA Consensus transcription factor motif database and Tabula Muris tissue single-cell RNA-seq signature database (C) as well as pathway enrichments for the Elsevier Pathway database and KEGG 2021 Human pathway database (D) (−log₁₀(p-values)), for the highly correlated (red) and anticorrelated (blue) proteins to 8 A_D metric. Databases were queried using Enrichr (Chen et al., 2013; Kuleshov et al., 2016).

Figure 5—figure supplement 1. Correlation reveals proteins highly associated with specific Ca²⁺ parameters.

Heatmap displaying unsupervised clustering of the correlation coefficients between the Z-scores for Ca²⁺ wave metrics and the Z-scores for normalized islet protein abundance. Islet proteins were quantified previously (Mitok et al., 2018). Perifusion conditions included 8 mM glucose (8G); 8G mM glucose + 1.25 mM L-alanine, 2 mM L-glutamine, and 0.5 mM L-leucine (8G/QLA); 8 mM glucose + QLA + 10 nM GIP (8G/QLA/GIP). Unsupervised clustering of the Ca²⁺ wave parameters revealed several parameters highly correlated to multiple insulin secretion conditions. Parameters included: average Ca²⁺ in 2 mM glucose (basal Ca²⁺), in 8 mM glucose (8G avg.), in 8G/QLA (8G/QLA avg), and in 8G/QLA/GIP (8G/QLA/GIP avg.); average detrended Ca²⁺ in 8 mM glucose (8G detr. avg.), in 8G/QLA (8G/QLA detr. avg), and in 8G/QLA/GIP (8G/QLA/GIP detr. avg.); average change in Ca²⁺ vs. basal in 8 mM glucose (8G avg. Δ vs. 2G), in 8G/QLA (8G/QLA avg. Δ vs. 2G), and in 8G/QLA/GIP (8G/QLA/GIP avg. Δ vs. 2G); change in detrended average Ca²⁺ vs. basal in 8 mM glucose (8G detr. Δ vs. 2G), in 8G/QLA (8G/QLA detr. Δ vs. 2G), and in 8G/QLA/GIP (8G/QLA/GIP detr. Δ vs. 2G); average oscillation peak Ca²⁺ in 8G (8G peak), in 8G/QLA (8G/QLA peak), and in 8G/QLA/GIP (8G/QLA/GIP peak); average oscillation baseline Ca²⁺ in 8G (8G baseline), in 8G/QLA (8G/QLA baseline), and in 8G/QLA/GIP (8G/QLA/GIP baseline); pulse duration in 8G (8G P_D), in 8G/QLA (8G/QLA P_D), and in 8G/QLA/GIP (8G/QLA/GIP P_D); active duration in 8G (8G A_D), in 8G/QLA (8G/QLA A_D), and in 8G/QLA/GIP (8G/QLA/GIP A_D); silent duration in 8 mM glucose (8G S_D), in 8G/QLA (8G/QLA S_D), and in 8G/QLA/GIP (8G/QLA/GIP S_D); plateau fraction in 8 mM glucose (8G P_F), in 8G/QLA (8G/QLA P_F), and in 8G/QLA/GIP (8G/QLA/GIP P_F); spectral density 1st component frequency in 8 mM glucose (8G 1st freq.), in 8G/QLA (8G/QLA 1st freq.), and in 8G/QLA/GIP (8G/QLA/GIP 1st freq.); spectral density 2nd component frequency in 8 mM glucose (8G 2nd freq.), in 8G/QLA (8G/QLA 2nd freq.), and in 8G/QLA/GIP (8G/QLA/GIP 2nd freq.); contribution of the 1st component to the Ca²⁺ waveform for 8 mM glucose (8G 1st freq. amp.), for 8G/QLA (8G/QLA 1st freq. amp.), and for 8G/QLA/GIP (8G/QLA/GIP 1st freq. amp.); and contribution of the 2nd component to the Ca²⁺ waveform for 8 mM glucose (8G 2nd freq. amp.), for 8G/QLA (8G/QLA 2nd freq. amp.), and for 8G/QLA/GIP (8G/QLA/GIP 2nd freq. amp.). Related to Figure 5.