Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
J Mol Med (Berl). 2020 Apr;98(4):451-467. doi: 10.1007/s00109-020-01887-x. Epub 2020 Feb 17.
The pancreatic islet is a dense cellular network comprised of several cell types with endocrine function vital in the control of glucose homeostasis, metabolism, and feeding behavior. Within the islet, endocrine hormones also form an intricate paracrine network with supportive cells (endothelial, neuronal, immune) and secondary signaling molecules regulating cellular function and survival. Modulation of these signals has potential consequences for diabetes development, progression, and therapeutic intervention. Beta cell loss, reduced endogenous insulin secretion, and dysregulated glucagon secretion are hallmark features of both type 1 and 2 diabetes that not only impact systemic regulation of glucose, but also contribute to the function and survival of cells within the islet. Advancing research and technology have revealed new islet biology (cellular identity and transcriptomes) and identified previously unrecognized paracrine signals and mechanisms (somatostatin and ghrelin paracrine actions), while shifting prior views of intraislet communication. This review will summarize the paracrine signals regulating islet endocrine function and survival, the disruption and dysfunction that occur in diabetes, and potential therapeutic targets to preserve beta cell mass and function.
胰岛是一个由多种具有内分泌功能的细胞类型组成的密集细胞网络，对于葡萄糖稳态、代谢和摄食行为的控制至关重要。在胰岛内，内分泌激素也与支持细胞（内皮细胞、神经元、免疫细胞）和调节细胞功能和存活的二级信号分子形成复杂的旁分泌网络。这些信号的调节可能对糖尿病的发展、进展和治疗干预有潜在的影响。β细胞的损失、内源性胰岛素分泌减少和胰高血糖素分泌失调是 1 型和 2 型糖尿病的标志性特征，不仅影响葡萄糖的全身调节，而且还影响胰岛内细胞的功能和存活。先进的研究和技术揭示了新的胰岛生物学（细胞特性和转录组），并确定了以前未被识别的旁分泌信号和机制（生长抑素和胃饥饿素的旁分泌作用），同时改变了先前对胰岛内通讯的看法。这篇综述将总结调节胰岛内分泌功能和存活的旁分泌信号，糖尿病中发生的破坏和功能障碍，以及保护β细胞数量和功能的潜在治疗靶点。
