Fig. 7: Improved insulin sensitivity by cotadutide results in reduced insulin secretory demand on the pancreatic β-cell. | Nature Communications

Fig. 7: Improved insulin sensitivity by cotadutide results in reduced insulin secretory demand on the pancreatic β-cell.

From: GLP-1R/GCGR dual agonism dissipates hepatic steatosis to restore insulin sensitivity and rescue pancreatic β-cell function in obese male mice

Fig. 7

Analysis of pancreatic function following 28-day treatment of cotadutide (10 nmol/kg, blue triangles), compared to vehicle (red circles). Reduction in body weight (BW) throughout the 28-day dosing period shown as % change (n = 8 mice per group) (A). Total pancreas weight (n = 8 mice per group) (B). Insulin levels in perfusate from isolated pancreatic islets across time (main) and the area under the curve (inset) (n = 8 mice per group) (C). Total pancreatic insulin content (D) or plasma insulin levels (n = 8 mice per group) (E). Total pancreatic glucagon content (n = 8 mice per group) (F) or plasma glucagon levels (n = 7 mice per group) (G). Quantification of β-cell mass (H), α-cell mass (I), or MAFA-positive staining nuclei (J) from multiplexed immunohistochemistry of pancreata. Representative images of immunohistochemistry. Biologic replicates are n = 8 mice per group. Technical replicates are n = 2 images per mouse. K. Quantification of mature granules (L) or immature granules (M) from electron microscopy of pancreatic β-cell islets. Biological replicates are n = 2 mice per group. Technical replicates are n = 29 (cotadutide) and n = 31 (vehicle) β-cells imaged per mouse. Representative images of electron microscopy (N). Two-way ANOVA with Tukey’s multiple comparisons post hoc (A), two-sided Student’s t-test (B, C (inset), D–J, L, M). Data shown as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < .0001. Exact p values are included in the Source Data file. Source data are provided as a Source Data file.

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