Fig. 4: Comparative actions of PG-102, semaglutide, and tirzepatide on β-cell function, cytoprotection, and peripheral glucose uptake.

a Glucose-stimulated insulin secretion from isolated mouse islets assessed using a perifusion system. Insulin secretion was monitored following a glucose shift (3–11 mM) in the presence of semaglutide, tirzepatide, or PG-102 (100 nM, left panel). Quantification of insulin secretion was performed by area under the curve (AUC; right panel). n = 4 independent islet preparations derived from different mice; each preparation was considered a biological replicate. b, c Cytoprotective and functional effects in INS-1 pancreatic β-cells exposed to streptozotocin (STZ). Cells were pretreated with the indicated agents (300 nM, 24 h) followed by exposure to STZ (10 nM, 3 h). b Cell viability assessed by MTS assay (n = 6 independent culture wells per group). (c) After 2-h glucose starvation, insulin secretion was measured following 30 min stimulation with 16.8 mM glucose using an ultrasensitive ELISA (n = 3 independent culture wells per group). Glucose uptake assessed by 2-NBDG uptake assay in differentiated 3T3-L1 adipocytes (n = 4 independent experiments) (d) and L6-GLUT4myc myotubes (n = 6 independent experiments) (e) following treatment with the indicated agents (300 nM). Data are presented as mean ± SEM. Statistical significance was evaluated using one-way ANOVA with Tukey’s post hoc test. AUC, area under the curve; STZ, streptozotocin; MTS, [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]; ELISA, enzyme-linked immunosorbent assay; 2-NBDG, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucoseSEM, standard error of the mean. Source data are provided as a Source data file.