ArticleMolecular biology reports2024
GLP-1 signaling-regulated SNAP25 is involved in improved insulin secretion in diabetic GK rats after Roux-en-Y gastric bypass surgery.
Article in Molecular biology reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 1 citations in OpenAlex.
- Histopathological and Transcriptomic Alterations in Metabolic Organs: A Case Study from a Spontaneously Diabetic Rhesus Macaque.International journal of molecular sciences · 2026Article
- GLP-1 agonists and the gut microbiome: A bidirectional relationship.British journal of clinical pharmacology · 2026Review
- Carbohydrate response element-binding protein (ChREBP) mediates decreased SNAP25 expression in islets from diabetic Goto-Kakizaki (GK) rats.FEBS open bio · 2024Article
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11 authors at 1 institution in 1 country.
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Abstract
backgroundRoux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved β-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of β-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND
resultsRYGB or sham surgery was conducted in GK rats. mRNA and protein expression of SNAP25 was assessed by qPCR and Western blot, respectively. Occupancy of CREB and acetyltransferase CBP and acetylation of histone H3 (ACH3) at the Snap25 promoter were determined using ChIP assay. RYGB led to increased SNAP25 expression and CREB phosphorylation in islets from GK rats. Increased SNAP25 improved GSIS in β-cells cultured in high glucose conditions. Consistent with increased plasma GLP-1 after RYGB, GLP-1R agonist exendin4 increased SNAP25 expression and CREB phosphorylation in β-cells. Mechanistically, exendin4 promoted the recruitment of CREB and CBP, thereby increasing ACH3 at the Snap25 promoter. Consistently, inhibition of CBP attenuated the effect of exendin4 on SNAP25 expression. Furthermore, the knockdown of SNAP25 diminished the increase of GSIS potentiated by chronic GLP-1 culture in INS-1 832/13 cells.
conclusionsOur findings unravel the novel mechanisms of RYGB-enhanced SNAP25 expression in β-cells, and SNAP25 may contribute to the improved β-cell secretory function induced by RYGB.
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