Journal: The Journal of Clinical Investigation

Article Title: β Cell Gαs signaling is critical for physiological and pharmacological enhancement of insulin secretion

doi: 10.1172/JCI183741

Figure Lengend Snippet: ( A – D ) Control ( n = 34) or Gnas βcell–/– ( n = 23) mice were treated with PBS, D-Ala2-GIP ( A and B ), or Ex4 ( C and D ) at t = –10 minutes. Mice were then challenged with i.p. glucose (1.5 g/kg) and iAUC presented from t = 0. Insulin secretion in D-Ala2-GIP–challenged ( B , n = 23,14) and Ex4-challenged ( D , n = 21,13) mice are shown at baseline ( t = 0) and 10 minutes after glucose challenge ( t = 10). Data are shown as mean ± SEM, * P < 0.05 as indicated. Data were analyzed by 2-way ANOVA of glycemic curves and insulin levels or 2-tailed Student’s t test of the iAUCs.

Article Snippet: Ex4 was purchased from MedChemExpress.

Techniques: Control

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Intraperitoneal administration of Rec2-exendin-4 normalizes metabolic function in Magel2- null mice (A) Amino acid sequence of exendin-4 transgene. (B) Experimental timeline of metabolic and behavioral parameters. (C) Body weight. (D) Area under the curve of body weight. (E) Weight gain. (F) Total weight gain. (G) Glucose tolerance test at 4 weeks post AAV injection. (H) Area under the curve of the glucose tolerance test. (I) Blood glucose after overnight fasting. (J) Relative fat mass as measured by EchoMRI at 8.5 weeks post AAV injection. (K) Relative lean mass as measured by EchoMRI at 8.5 weeks post injection. Data are means ± SEM. Sample size: WT GFP n = 6, WT Ex4 n = 5, Magel2 -null GFP n = 5, Magel2 -null Ex4 n = 7. Individual values are shown in graph. Two-way ANOVAs with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01 , ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, ns, not significant. Scatterplots not connected by same letter are significantly different.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques: Sequencing, Injection

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 gene therapy reverses genotype-driven fat mass increase in Magel2- null mice (A) Body weight at time of euthanasia. (B) Brown adipose tissue (BAT) weight. (C) Inguinal white adipose tissue (iWAT) weight. (D) Epididymal white adipose tissue (eWAT) weight. (E) Retroperitoneal white adipose tissue (rWAT) weight. (F) Liver weight. (G) Pancreas weight. (H) Gastrocnemius muscle weight. Data are means ± SEM. Sample size: WT GFP n = 6, WT Ex4 n = 5, Magel2 -null GFP n = 5, Magel2 -null Ex4 n = 7. Individual values are shown in graph. Two-way ANOVAs with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01 , ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, ns, not significant. Scatterplots not connected by same letter are significantly different.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques:

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 gene therapy improves circulating markers of systemic metabolism in Magel2 -null mice (A) Serum exendin-4. ∗ p < 0.05 WT-Ex4 versus Magel2 -null Ex4. (B) Serum glucose (C) Serum insulin. (D) Homeostatic model assessment for insulin resistance index (HOMA-IR). (E) Serum leptin. (F) Serum adiponectin. (G) Adiponectin to leptin ratio (with adiponectin level expressed in μg/mL and leptin level expressed in ng/mL). (H) Serum triglyceride. (I) Serum alanine transaminase (ALT). (J) Serum aspartate transferase (AST). Data are means ± SEM. Sample size: WT GFP n = 6, WT-Ex4 n = 5, Magel2 -null GFP n = 5, Magel2 -null Ex4 n = 7. Individual values are shown in graph. Two-way ANOVAs with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01 , ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, ns not significant. Scatterplots not connected by same letter are significantly different.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques:

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 gene therapy regulates adipose gene expression in Magel2 -null mice (A) Epididymal white adipose tissue (eWAT) gene expression. (B) Brown adipose tissue (BAT) gene expression. Data are means ± SEM. Sample size: n = 5 per group. Individual values are shown in graph. Two-way ANOVAs with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01 ∗∗∗ p < 0.001, ns, not significant; p values trending toward significance were shown where applicable. Scatterplots not connected by same letter are significantly different.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques: Gene Expression

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 gene therapy alters hypothalamic and hepatic gene expression in Magel2 -null mice (A) Hypothalamic gene expression. (B) Liver gene expression. Data are means ± SEM. Sample size: n = 5 per group. Individual values are shown in graph. Two-way ANOVAs with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01 ∗∗∗∗ p < 0.0001, ns, not significant; p values trending toward significance were shown where applicable. Scatterplots not connected by same letter are significantly different.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques: Gene Expression

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 gene therapy improves metabolic and behavioral functions in diet-induced obesity model (5 months study) (A) Body weight. (B) Total weight gain of 5 months. (C) Average food intake measured week 1–5 post AAV injection. (D) Absolute fat mass and absolute lean mass at 5 weeks post AAV injection. (E) Relative fat mass and relative lean mass at 5 weeks post AAV injection. (F) Glucose tolerance test at 6 weeks post AAV injection. (G) Area under the curve of the glucose tolerance test. (H) Open field test at 13 weeks post AAV injection. (I) Novel object recognition test at 13 weeks post AAV injection. (J) H&E staining of livers. Data are means ± SEM. Sample size: n = 5 per group. Individual values are shown in graph. Time course data (body weights and GTT) were analyzed using two-way RM-ANOVA with Sidak’s multiple comparisons test. Unpaired t test for other data analyses. ∗ p < 0.05, ∗∗ p < 0.01 , ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001. Scale bars, 100 μm.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques: Injection, Staining

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 and Rec2-exendin-4-HA reverses diet-induced obesity and associated metabolic dysfunction (A) Body weight. Mixed ANOVA with Sidak’s multiple comparisons test. ∗ p < 0.05 Ex4 and Ex4-HA versus GFP. (B) Final body weight. (C) Weight gain. Two-way RM-ANOVA with Sidak’s multiple comparisons test. ∗∗∗ p < 0.001 Ex4 and Ex4-HA versus GFP. (D) Total weight gain. (E) Average food intake measured week 1–4 post AAV injection. (F) Glucose tolerance test at 6 weeks post AAV injection. (G) Area under the curve of the glucose tolerance test. (H) Indirect calorimetry at 7–8 weeks post injection. Data are means ± SEM. Sample size: GFP n = 4, Ex4 n = 5, Ex4-HA n = 5. Individual values are shown in graph. One-way ANOVA with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01 , ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques: Injection

Journal: Molecular Therapy Advances

Article Title: Low dose systemic AAV-exendin-4 gene therapy for Prader-Willi syndrome and dietary obesity

doi: 10.1016/j.omta.2026.201718

Figure Lengend Snippet: Rec2-exendin-4 and Rec2-exendin-4-HA alleviates obesity-associated fatty liver, insulin resistance, and hyperleptinemia (A) Tissue mass. BAT, brown adipose tissue; eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; rWAT, retroperitoneal white adipose tissue. (B) Serum glucose. (C) Serum insulin. (D) Homeostatic model assessment for insulin resistance index (HOMA-IR). (E) Serum leptin. (F) Serum adiponectin. (G) Adiponectin to leptin ratio (with adiponectin level expressed in μg/mL and leptin level expressed in ng/mL). (H) Serum triglyceride. (I) Hepatic triglyceride. (J) Serum exendin-4. ∗ p < 0.05 Ex4 versus Ex4-HA. (K) Western blotting of liver and eWAT samples from Ex4-HA group. (L) Quantification of western blotting in (K). Data are means ± SEM. Sample size: GFP n = 4, Ex4 n = 5, Ex4-HA n = 5. Individual values are shown in graph. One-way ANOVA with Tukey’s post hoc test to adjust pairwise comparisons of all groups. ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Article Snippet: Exendin-4 (Ex4) is a peptide isolated from the venom of Gila monster which has 53% homology with the biological active form of GLP-1(7–37), but acts as a full agonist of GLP-1R and therefore has been developed as a drug for diabetes., To assess the therapeutic potential of a systemic incretin mimetics gene therapy as a novel, long lasting, and safe treatment for PWS obesity, we designed a transgene of Ex4 whose peptide product can be secreted from transduced cells.

Techniques: Western Blot