Bisht Shradha, Singh Mamta F
Amity Institute of Pharmacy, Amity University, Lucknow, Uttar Pradesh, India.
School of Pharmaceutical Sciences, SBS University, Balawala, Uttarakhand, India.
Arch Physiol Biochem. 2024 Dec;130(6):854-865. doi: 10.1080/13813455.2023.2299920. Epub 2024 Jan 9.
Insulin secretion is a highly regulated process critical for maintaining glucose homeostasis. This abstract explores the intricate interplay between three essential pathways: The Triggering Pathway, The Metabolic Amplifying Pathway, and Cellular Transduction, in orchestrating glucose-dependent biphasic insulin secretion.
During the triggering pathway, glucose metabolism in pancreatic beta-cells leads to ATP production, closing ATP-sensitive potassium channels and initiating insulin exocytosis. The metabolic amplifying pathway enhances insulin secretion via key metabolites like NADH and glutamate, enhancing calcium influx and insulin granule exocytosis. Additionally, the cellular transduction pathway involves G-protein coupled receptors and cyclic AMP, modulating insulin secretion.
These interconnected pathways ensure a dynamic insulin response to fluctuating glucose levels, with the initial rapid phase and the subsequent sustained phase. Understanding these pathways' complexities provides crucial insights into insulin dysregulation in diabetes and highlights potential therapeutic targets to restore glucose-dependent insulin secretion.
胰岛素分泌是维持葡萄糖稳态的关键且高度受调控的过程。本摘要探讨了三条重要途径之间复杂的相互作用:触发途径、代谢放大途径和细胞转导途径,它们共同协调葡萄糖依赖性双相胰岛素分泌。
在触发途径中,胰腺β细胞中的葡萄糖代谢导致ATP生成,关闭ATP敏感性钾通道并启动胰岛素胞吐作用。代谢放大途径通过NADH和谷氨酸等关键代谢物增强胰岛素分泌,增加钙内流和胰岛素颗粒胞吐作用。此外,细胞转导途径涉及G蛋白偶联受体和环磷酸腺苷,调节胰岛素分泌。
这些相互关联的途径确保了胰岛素对波动的葡萄糖水平产生动态反应,包括初始的快速阶段和随后的持续阶段。了解这些途径的复杂性为深入了解糖尿病中胰岛素调节异常提供了关键见解,并突出了恢复葡萄糖依赖性胰岛素分泌的潜在治疗靶点。