Fig. 8: SMOC1 protein reduces GSIS, INS expression, Ca2+ flux, intracellular cAMP formation and insulin granule maturation.
a Circulating levels of SMOC1 in non-diabetic (n = 5) and T2D subjects (n = 4). b Effect of rhSMOC1 on insulin secretion in human islets from adult non-diabetic donors (ratio of insulin secretion at 16 mM and 5.5 mM per insulin content) (n = 3 different human islet preparations). c Insulin secretion (ratio of insulin secretion at 20 mM and 2 mM corrected by insulin content) (left) and INS expression by qPCR (right) in EndoC-βH1 cells (n = 8 experiments) treated with different doses of rhSMOC1 protein. d Measurement of calcium flux in EndoC-βH1 cells transduced with adenovirus-GCaMP5, treated with 1000 ng/ml rhSMOC1 for 48 h and exposed to 2 and 20 mM glucose in a perfusion system (n = 3, representative tracking from a single experiment is shown). Quantitation of area under the curve (AUC) of 30-40 cells in these experiments (right). e Intracellular cAMP levels in EndoC-βH1 cells treated with 1000 ng/ml rhSMOC1 and exposed to 2 and 20 mM glucose or 10 nM exendin-4 for 1 h (n = 4 independent replicates). f Electron microscopy of human islet cells treated with 1000 ng/ml rhSMOC1 for 48 h. Representative images focus on human β-cells showing mature insulin granules (MIG) and immature insulin granules (IIG); mature granules contain cores of condensed insulin with angular sides and large surrounding halos. Immature granules are situated mainly near the trans-Golgi network and have no halos. Quantitation of the number of MIG and IIG in n = 3 independent biological replicates per condition (right). g Schematic representation of the effects of SMOC1 in human β-cells. Created in BioRender. Garcia-Ocana, A. (2025) https://BioRender.com/nizfh1l. In all the panels, bars indicate mean+ SEM, *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001 or as indicated in the figure, using two-tailed Student’s t-test.
