Fig. 3: Tirzepatide stimulates glucagon secretion in human islets.
From: The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets
a, Glucagon secretion from human islets stimulated with either 30 nM hGIP or GLP-1 individually (minutes 8–24) or together (minutes 32–50) under 16 mM glucose conditions. The iAUC was calculated for the individual effects of the peptides (minutes 8–24) and the combined effects (minutes 32–50) using the value of the first time point as the baseline. GIP, n = 4; GLP-1, n = 6; GIP + GLP-1, n = 10. b, Glucagon secretion from human islets treated with 30 nM of either hGIP or tirzepatide (TZP) under 16 mM glucose conditions. The iAUC was calculated using minutes 24 and 54 as the baseline values for the first and second stimulation, respectively. n = 3 for all groups. c, Glucagon secretion in response to 30 nM TZP in eight individual donor sets of human islets under 16 mM glucose conditions. The summary of these experiments is shown as the of the average values from minutes 55–65. The fold induction on the right y axis was calculated using the baseline glucagon values from minutes 35–45. n = 3 for each donor, n = 8 for summary data. d, Glucagon secretion in human islets (donor R464) stimulated with TZP (30 nM) at either 2.7 mM glucose (2.7 G) or 10 mM glucose (10 G), with or without 3 mM alanine. n = 3. e, Somatostatin concentrations from pooled samples taken from baseline samples or during TZP stimulation. n = 3. All values are mean ± s.e.m. Statistical tests were one-way ANOVA with Tukey’s post-hoc test (a), two-way ANOVA with Sidak post-hoc test (b), paired t-test (c,d) and unpaired t-test (e).
