Secretory granule exocytosis and its amplification by cAMP in pancreatic β-cells
Secretory granule exocytosis and its amplification by cAMP in pancreatic β-cells
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胰腺 β 细胞中分泌颗粒的胞吐作用及其 cAMP 的扩增
DOI：
10.1007/s13340-022-00580-3
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发表时间：
2022
影响因子：
2.2
通讯作者：
Lena Eliasson
中科院分区：
文献类型：
--
作者：
Mototsugu Nagao;Jens O. Lagerstedt;Lena Eliasson
胰腺β细胞响应葡萄糖而分泌胰岛素的事件序列被称为“刺激-分泌耦合”。刺激-分泌耦合的核心是响应葡萄糖摄取而产生电活动并引起Ca2+振荡以触发含胰岛素分泌颗粒的胞吐作用的过程。在胞吐作用之前，分泌颗粒被动员并停靠在质膜上，并准备与质膜融合。连同最终与质膜的融合，这些步骤被称为胰岛素分泌的胞吐过程。胞吐过程中涉及的步骤对于 β 细胞释放胰岛素至关重要，并且被认为对于葡萄糖稳态至关重要。我们最近证实了患有 2 型糖尿病 (T2D) 的肥胖捐献者的人类胰岛和 β 细胞中胞吐作用过程缺陷的特征。此外，环磷酸腺苷 (cAMP) 通过加速胞吐过程等机制增强葡萄糖刺激的胰岛素分泌。在这篇小综述中，我们的目的是整理有关分泌颗粒胞吐作用及其 cAMP 扩增的基本知识。然后，我们建议脂肪酸转位酶 CD36 作为 β 细胞中引起胞吐作用缺陷的诱因，这被认为是与肥胖相关的 T2D 发病机制。最后，我们提出了基于 CD36 中和抗体和载脂蛋白 A-I (ApoA-I) 的胞吐作用缺陷的潜在疗法，以改善 T2D 中的 β 细胞功能。
The sequence of events for secreting insulin in response to glucose in pancreatic β-cells is termed “stimulus-secretion coupling”. The core of stimulus-secretion coupling is a process which generates electrical activity in response to glucose uptake and causes Ca2+oscillation for triggering exocytosis of insulin-containing secretory granules. Prior to exocytosis, the secretory granules are mobilized and docked to the plasma membrane and primed for fusion with the plasma membrane. Together with the final fusion with the plasma membrane, these steps are named the exocytosis process of insulin secretion. The steps involved in the exocytosis process are crucial for insulin release from β-cells and considered indispensable for glucose homeostasis. We recently confirmed a signature of defective exocytosis process in human islets and β-cells of obese donors with type 2 diabetes (T2D). Furthermore, cyclic AMP (cAMP) potentiates glucose-stimulated insulin secretion through mechanisms including accelerating the exocytosis process. In this mini-review, we aimed to organize essential knowledge of the secretory granule exocytosis and its amplification by cAMP. Then, we suggest the fatty acid translocase CD36 as a predisposition in β-cells for causing defective exocytosis, which is considered a pathogenesis of T2D in relation to obesity. Finally, we propose potential therapeutics of the defective exocytosis based on a CD36-neutralizing antibody and on Apolipoprotein A-I (ApoA-I), for improving β-cell function in T2D.