Figure 6.

SCD1−/− knockout in mouse affects the morphology of insulin- and glucagon-containing granules in pancreatic islets, exaggerates basal glucagon release, and disturbs insulin secretion processes. (A, H) Ultrastructure of insulin (A) and glucagon (I) secretory granules in individual pancreatic β-cells and α-cells in WT and SCD1−/− mice that were fed a chow or HF diet. Blue-framed and green-framed insets show the morphology of mature insulin granule and glucagon granule, respectively. All images are at the same magnification. (B, C, J, K) Size (n = 100) and density (n = 5) of insulin (B, C) and glucagon (J, K) secretory granules in the cytoplasm of single β-cells and α-cells. The number of insulin/glucagon granules was calculated per 10 μm² of the cytoplasm. (E) Ultrastructure of immature insulin secretory granules in individual β-cells in WT and SCD1−/− mice that were fed a chow or HF diet. Yellow-framed insets show the ultrastructure of immature insulin granule. Red arrows indicate immature insulin granules that were identified in the cell. Density of vesicles that contain proinsulin in the cytoplasm of single β-cells (n = 5). The number of immature insulin granules was calculated per 100 μm² of the cytoplasm. ∗p < 0.05, ∗∗p < 0.005, vs. WT chow; ^#p < 0.05, vs. SCD1−/− chow. ns, nonsignificant. (G) mRNA levels of Pcsk1, Pcsk2 and Cpe genes in pancreatic islets from WT and SCD1−/− mice. ∗p < 0.05, vs WT Chow. (D, G, L) Secretion of insulin (D), proinsulin (G), and glucagon (L) from pancreatic islets in WT and SCD1−/− mice that were fed a chow or HF diet. n = 3. LG, low glucose concentration (2.75 mM); HG, high glucose concentration (16.5 mM). ∗p < 0.05, ∗∗p < 0.005, vs. WT chow HG; ^&p < 0.05, vs. WT chow LG; ˆp < 0.05, vs. SCD1−/− chow LG; ^#p < 0.05, vs. SCD1−/− chow HG. The results are expressed as mean ± SD.