Diabetes, Obesity, and Metabolism Institute, Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
The Microscopy CoRE and Advanced Bioimaging Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sci Adv. 2020 Oct 9;6(41). doi: 10.1126/sciadv.aaz9124. Print 2020 Oct.
Understanding the detailed anatomy of the endocrine pancreas, its innervation, and the remodeling that occurs in diabetes can provide new insights into metabolic disease. Using tissue clearing and whole-organ imaging, we identified the 3D associations between islets and innervation. This technique provided detailed quantification of α and β cell volumes and pancreatic nerve fibers, their distribution and heterogeneity in healthy tissue, canonical mouse models of diabetes, and samples from normal and diabetic human pancreata. Innervation was highly enriched in the mouse endocrine pancreas, with regional differences. Islet nerve density was increased in nonobese diabetic mice, in mice treated with streptozotocin, and in pancreata of human donors with type 2 diabetes. Nerve contacts with β cells were preserved in diabetic mice and humans. In summary, our whole-organ assessment allows comprehensive examination of islet characteristics and their innervation and reveals dynamic regulation of islet innervation in diabetes.
了解内分泌胰腺的详细解剖结构、其神经支配以及糖尿病发生的重塑，可以为代谢性疾病提供新的见解。我们使用组织透明化和全器官成像技术，确定了胰岛和神经支配之间的 3D 关联。这项技术详细量化了α和β细胞体积以及胰腺神经纤维的分布和异质性，包括健康组织、经典的糖尿病小鼠模型以及来自正常和糖尿病人类胰腺的样本。在小鼠的内分泌胰腺中，神经支配非常丰富，存在区域差异。非肥胖型糖尿病小鼠、链脲佐菌素处理的小鼠以及 2 型糖尿病患者的胰腺中，胰岛神经密度增加。β细胞与神经的接触在糖尿病小鼠和人类中得以保留。总之，我们的全器官评估允许对内分泌胰腺的特征及其神经支配进行全面检查，并揭示了糖尿病中胰岛神经支配的动态调节。
