Research Article: Shenqi compound enhances pancreatic ?-cell secretion by promoting the maturation and transport of insulin secretory vesicles through the NOD1/RIP2 signaling pathway
Abstract:
Shenqi compound (SQC) is an effective prescription in Chinese medicine to enhance glucose homeostasis and protect pancreatic cells from high glucose-induced damage. However, the protection mechanism remains unclear.
To investigate the effect of SQC on INS-1 cell secretion and evaluate the associated mechanisms.
INS-1 cells were cultured in serum augmented with or without NOD1 inhibitor ML130 (2?M) for 1 h, then exposed into a high glucose (50 mM) condition to simulate type 2 diabetes mellitus (T2DM) for 24 h and treated with different concentrations (0, 5, 10, 15, 20%) of SQC in serum for another 24 h. Then, the cell counting kit-8 (CCK-8) method, glucose-stimulated insulin secretion (GSIS) assay, transmission electron microscopy (TEM), real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot were performed for further investigation.
Under high glucose conditions, 15% SQC was the optimal therapeutic concentration, significantly improved INS-1 cell viability ( p = 0.032) and enhanced insulin secretion ( p < 0.0001). Ultrastructural analysis showed that after high glucose stimulation in GSIS, especially at 20 min, 15% SQC significantly increased both the total density ( p = 0.143) and the mature ratio ( p = 0.003) of insulin secretory vesicles. Furthermore, 15% SQC facilitated the dynamic transport of vesicles toward the cell membrane, evidenced by an increased vesicle density within 300 nm of the membrane at 10 min, followed by a subsequent decrease at 20 min—a trend consistent with that observed in the control group. Moreover, at the molecular level, 15% SQC intervention markedly up-regulated NOD1 and RIP2 protein expression ( p = 0.029 and p < 0.0001) and transcription ( p = 0.886 and p = 0.393) levels, while ML130 reversed the activation of the NOD1/RIP2 pathway.
SQC promotes the maturation and transport of insulin secretory vesicles, thereby enhancing the secretory function of INS-1 cells in response to high glucose-induced damage. This protective effect may be associated with the activation of the NOD1/RIP2 signaling pathway.
Introduction:
Shenqi compound (SQC) is an effective prescription in Chinese medicine to enhance glucose homeostasis and protect pancreatic cells from high glucose-induced damage. However, the protection mechanism remains unclear.
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