National Engineering Research Center for Functional Food, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, China.
Food Funct. 2024 Oct 14;15(20):10316-10322. doi: 10.1039/d4fo01290a.
Glucagon-like peptide-1 (GLP-1) plays a crucial role in regulating glucose homeostasis by stimulating insulin secretion and suppressing glucagon release. Our previous study observed that pea protein hydrolysate (PPH) exhibited the function of triggering GLP-1 secretion. However, the underlying mechanisms have not been revealed. Herein, the mechanisms of PPH-stimulated GLP-1 secretion were investigated in NCI-H716 cells. The PPH-induced GLP-1 secretion was reduced ( < 0.05) after adding the sensing receptor antagonists NPS-2143 and 4-AMBA, indicating that activation of both calcium-sensing receptor (CaSR) and peptide-transporter 1 (PepT1) was involved in PPH-triggered GLP-1 release. Moreover, the intracellular Ca level increased by 2.01 times during the PPH-induced GLP-1 secretion. Similarly, the cAMP content also increased by 1.43 times after stimulation by PPH. The RT-qPCR results showed that PPH increased the gene expression of prohormone convertase 1/3 (PCSK-1) by 2.79-fold, which effectively promoted the conversion of proglucagon (GCG) to GLP-1. The specific pathway of PPH-induced GLP-1 secretion may involve both CaSR and PepT1 activation-induced Ca influx and cAMP generation, which effectively enhanced the enzyme activity of prohormone convertase 1/3 (PCSK-1) and ultimately promoted GLP-1 secretion.
胰高血糖素样肽-1（GLP-1）通过刺激胰岛素分泌和抑制胰高血糖素释放，在调节葡萄糖稳态方面发挥着关键作用。我们之前的研究观察到，豌豆蛋白水解物（PPH）具有触发 GLP-1 分泌的功能。然而，其潜在机制尚未被揭示。本研究旨在探究 PPH 刺激 GLP-1 分泌的机制。在 NCI-H716 细胞中，我们发现加入感应受体拮抗剂 NPS-2143 和 4-AMBA 后，PPH 诱导的 GLP-1 分泌减少（<0.05），这表明钙敏感受体（CaSR）和肽转运蛋白 1（PepT1）的激活均参与了 PPH 触发的 GLP-1 释放。此外，PPH 诱导 GLP-1 分泌过程中细胞内 Ca 水平增加了 2.01 倍。同样，PPH 刺激后 cAMP 含量也增加了 1.43 倍。实时定量 PCR 结果显示，PPH 使前激素转化酶 1/3（PCSK-1）的基因表达增加了 2.79 倍，这有效地促进了胰高血糖素原（GCG）向 GLP-1 的转化。PPH 诱导 GLP-1 分泌的特定途径可能涉及 CaSR 和 PepT1 激活诱导的 Ca 内流和 cAMP 生成，这有效地增强了前激素转化酶 1/3（PCSK-1）的酶活性，最终促进了 GLP-1 的分泌。
