Fig. 4

In vitro efficacy of chimeric GLP-1A for ASBT-mediated endocytosis and insulinotropic effect. A Scheme of the cellular uptake mechanism for GLP-1A and oligomeric DOCA-G1As utilizing ASBT-mediated endocytosis, leading to the formation of ASBT vesicles in cytosol. B Cellular permeability in Caco-2 cells after treatment with 1 μM of exenatide, mD-G1A, bD-G1A, and tD-G1A (n = 3; data are presented as means ± standard deviations). ^*p < 0.05 and ^***p < 0.001 compared with exenatide. C Relative P_app of oligomeric DOCA-G1A in the presence of actinomycin D (Act D) alone, clofazimine (CFZ) alone, or both (Act D + CFZ) (n = 4; data are presented as means ± standard deviations). ^***p < 0.001 compared with relative P_app of the non-treated group. D ASBT distribution from the membrane and cytoplasm after administration of 1 μM of tD-G1A. E Relative signal intensity of ASBT in membrane and cytoplasm. ASBT quantification was conducted using ImageJ software (n = 3; data are presented as means ± standard deviations). ^**p < 0.01 and ^***p < 0.001 compared with the control. F Scheme of GLP-1R binding of oligomeric DOCA-G1A. G Insulin secretion (n = 4; data are presented as means ± standard deviations) by islet β cells in low-glucose (2.8 mM) and high-glucose (28 mM) conditions after drug treatment [non-treated; exenatide, 5 nM (control); GLP-1A-Cys, 5 nM; mD-G1A, 5 nM; bD-G1A, 5 nM; tD-G1A, 5 nM] and H the secretion index. ^*p < 0.05, ^**p < 0.01, and ^***p < 0.001 compared with exenatide