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. 2024 Oct 20;90:102050. doi: 10.1016/j.molmet.2024.102050

Figure 1.

Figure 1

Loss of glucagon action augments delta cell proliferation and mass expansion in mouse and transplanted human islets. (A) Representative images of pancreatic islet and delta cell proliferation in 8 week old Gcg+/+/Gcg−/− (upper row) and 2 week treated IgG/GCGR-Ab-treated C57BL6 (bottom row) mice. Somatostatin (green), Ki67 (red), and DAPI (blue) are shown. White arrows indicate Ki67+ somatostatin + cells. (B, C) Quantification of pancreatic islet delta cell proliferation in (B) Gcg+/+ (black bar) and Gcg−/− (red bar) mice (n = 1–2 females and 2–3 males per genotype) and (C) control IgG (black bar) and GCGR-Ab-treated (blue bar) mice (all males, unpaired t test, ∗∗∗p < 0.001 versus Gcg+/+, ∗∗p < 0.01 versus IgG). (D) Representative images of pancreatic islet hormones in Gcg+/+/Gcg−/− (upper row) and IgG/GCGR-Ab-treated (bottom row) mice. Insulin (green), somatostatin (red), and pro-glucagon (Gcg+/+/Gcg−/−; blue) or glucagon (IgG/GCGR-Ab; blue) are shown. (E, F) Pancreatic islet delta cell mass in (E) Gcg+/+ (black bar) and Gcg−/− (red bar) mice (n = 1–2 females and 3 males per genotype) and (F) control IgG (black bar) and GCGR-Ab-treated (blue bar) mice (all males, unpaired t test, ∗∗p < 0.01 versus Gcg+/+ or IgG). (G) Schematic of approach for human islet subcapsular renal transplantation in NSG recipient mice followed by control IgG or GCGR-Ab treatment. Created with BioRender.com (H) Representative images of delta cell proliferation in human islet grafts after 4 weeks of control IgG (upper row) or GCGR-Ab-treatment (bottom row). Grafts were immunostained for somatostatin (green), Ki67 (red), and DAPI (blue). White dashed boxes indicate regions selected for insets. (I) Quantification of delta cell proliferation in transplanted human islets in control IgG (black circles) and GCGR-Ab-treated (orange circles) mice (n = 3 donors [see Supplemental Table 1], unpaired t test, ∗∗p < 0.01 versus IgG).