exendin-4 ex4  (ApexBio)

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: JCI Insight

Article Title: A splice site variant in MADD affects hormone expression in pancreatic β cells and pituitary gonadotropes

doi: 10.1172/jci.insight.167598

Figure Lengend Snippet: ( A ) Schematic of SC-islet differentiation protocol. ( B ) PDX1 , ( C ) NKX2-2 , ( D ) SOX9 , and ( E ) NKX6-1 mRNA levels in WT and dex30 cultures at stages 3–5, relative to undifferentiated stem cells ( n = 4–6 for WT, n = 8–11 for dex30 ). ( F ) INS , ( G ) PCSK1 , and ( H ) PCSK2 mRNA levels in WT and dex30 cultures at stages 6–7, relative to undifferentiated stem cells ( n = 6 for WT, n = 9 for dex30 at ST6, n = 10 for WT, and n = 13–14 for dex30 at stage 7). ( I ) Total insulin and ( J ) proinsulin content in WT and dex30 SC-islets at stage 7 ( n = 7–9 for WT, n = 9–12 for dex30 ). ( K ) Proinsulin-to-insulin ratio in WT and dex30 SC-islets at stage 7 ( n = 7 for WT, n = 9 for dex30 ). ( L ) Static insulin secretion from WT and dex30 SC-islets at stage 7, in 2.8 mM glucose (G2.8), 16.8 mM glucose (G16.8), 16.8 mM glucose + 50 mM Exendin 4 (Ex4), and 2.8 mM glucose with 30 mM KCl ( n = 5 for WT, n = 6 for dex30 ). ( M ) Dynamic insulin secretion in WT and dex30 SC-islets at stage 7. Conditions like in L ( n = 7 for WT, n = 9 for dex30 ). ( N ) Area under curve quantification of dynamic insulin secretion in M . *** P < 0.001, ** P < 0.01, and * P < 0.05 analyzed by Student’s t test ( I – K and N ) or multiple t tests ( B – H and L ).

Article Snippet: A total of 150 SC-islets were handpicked to 12-well plates and equilibrated in Krebs-Ringer buffer (KRB) with 2.8 mM glucose for 90 minutes, then subjected to sequential 30-minute incubations of 2.8 mM glucose, 16.8 mM glucose, 16.8 mM glucose + 50 ng/mL Ex4 (Tocris), and 2.8 mM glucose + 30 mM KCl in KRB.

Techniques:

Journal: Molecules and Cells

Article Title: ER stress and unfolded protein response (UPR) signaling modulate GLP-1 receptor signaling in the pancreatic islets

doi: 10.1016/j.mocell.2023.12.002

Figure Lengend Snippet: Acute ER stress triggers GLP-1R signaling use of Gq. (A-D) Isolated mouse islets were pretreated with tunicamycin (Tm, 1 μg/ml, 8 hours) and further administered with MDL-12330A (MDL, adenylyl cyclase inhibitor, 10 μM) (A, B) or YM-254890 (YM, Gq inhibitor, 200 nM) (C, D) along with exendin-4 (Ex4, 50 nM) and high glucose (Glc, 17 mM) for an additional 1 hour. (A, C) Insulin secretion and (B, D) its fold change. Data are presented as means ± SEM (n = 4). Statistical analyses were performed using either 1-way ANOVA followed by Holm-Sidak’s test (A, C) or unpaired t-tests with Welch’s correction (B, D). ns, non-significance. * P < .05, ** P < .01, *** P < .001.

Article Snippet: Exendin-4 (Ex4) was obtained from Merck (E7144), whereas IXA4 was purchased from DC Chemicals (Cat no. DC51012).

Techniques: Isolation

Journal: Molecules and Cells

Article Title: ER stress and unfolded protein response (UPR) signaling modulate GLP-1 receptor signaling in the pancreatic islets

doi: 10.1016/j.mocell.2023.12.002

Figure Lengend Snippet: 4-PBA, a chemical chaperone, promotes GLP-1R agonist-induced insulin secretion and GLP-1R’s Gq utilization in ER stress-experiencing and db/db islets. (A, B) Islet insulin secretion. Isolated lean mouse islets were sequentially treated with 4-PBA (2.5 mM, 24 hours), tunicamycin (1 μg/ml, 8 hours), and high glucose (Glc, 17 mM, 1 hour) with or without Ex4 (50 nM), YM (200 nM), and MDL (10 μM). (C-E) Islets were isolated from 12-week-old db/db mice and then pretreated with 4-PBA (2.5 mM, 24 hours) before high glucose with indicated reagents. (C) Insulin secretion and (D, E) its fold change. Data are presented as means ± SEM (n = 4). Statistical analyses were performed using either unpaired t-tests (A, D, E) or 1-way ANOVA (B, C). ns, non-significance. * P < .05, ** P < .01, *** P < .001.

Article Snippet: Exendin-4 (Ex4) was obtained from Merck (E7144), whereas IXA4 was purchased from DC Chemicals (Cat no. DC51012).

Techniques: Isolation