Extended Data Fig. 4: HK1 expression is present in the beta-cells of donors with HK1-CHI, but not ABCC8-Hyperinsulinism or Non-HI controls.
a) Confocal imaging of HK1 (red); glucagon (yellow); insulin (cyan) and DAPI (dark blue) in pancreatic tissue resected from patient 6 (Supplementary Table 2) with a HK1 variant. HK1 co-localises with insulin, but not with glucagon. Staining in tissue resected from an individual with ABCC8-Hyperinsulinism (HI-control) and a non-HI control, showed no expression of HK1 in either alpha (glucagon-positive) or beta (insulin-positive cells). Scale bar – 100 µm. b) Enlarged image of a portion of the islet shown in (a) from an individual with HK1-HI (Patient 6). This image confirms the expression of HK1 specifically in beta cells (white arrows) and absence of HK1 in alpha cells (orange arrows). Scale bar – 20 µm. c) HK1 expression (Median fluorescence intensity (MFI)) is higher in the HK1-HI donor beta-cells within HK1 positive islets, when compared to alpha cells (Patient 1 - beta-cells (n = 1580); alpha-cells (n = 161); and Patient 6 - beta-cells (n = 2284); alpha-cells (n = 9321)). Two-tailed Mann-Whitney (****p < 0.0001), p < 3.2 × 10−9 and p < 6.4 × 10−172 for Patient 1 and Patient 6 respectively. This suggests the impact of the HK1 variant is beta-cell specific. Violin plots shown with the median (dashed line) and IQR (dotted lines) presented. Source data provided in Supplementary Information.
