Connectomics Research Center, National Tsing Hua University, Hsinchu, Taiwan.
Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
Diabetologia. 2018 Jan;61(1):168-181. doi: 10.1007/s00125-017-4409-x. Epub 2017 Aug 29.
AIMS/HYPOTHESIS: Identification of a pancreatic neuro-insular network in mice suggests that a similar integration of islets and nerves may be present in the human pancreas. To characterise the neuro-insular network and the intra-pancreatic ganglia in a clinically related setting, we examined human pancreases in health and with fatty infiltration via 3-dimensional (3D) histology and compared the human pancreatic microenvironment with its counterpart in mice.
Human pancreatic specimens from individuals with normal BMI, high BMI (≥ 25) and type 2 diabetes were used to investigate the neuro-insular network. Transparent specimens were prepared by tissue clearing for transmitted light and deep-tissue fluorescence imaging to simultaneously visualise infiltrated adipocytes, islets and neurovascular networks.
High-definition images of human islets reveal that both the sympathetic and parasympathetic nerves enter the islet core and reside in the immediate microenvironment of islet cells. Around the islets, the neuro-insular network is visualised with 3D histology to identify the intra-pancreatic ganglia (peri-lobular and intra-parenchymal ganglia) and the islet-ganglionic association. In humans, but not in mice, pancreatic fatty infiltration (BMI dependent) features adipocytes infiltrating into the parenchyma and accumulating in the peri-lobular space, in which the peri-lobular ganglia also reside. We identified the formation of adipose-ganglionic complexes in the peri-lobular space and enlargement of ganglia around adipocytes. In the specimen from the individual with type 2 diabetes, an increase in the number of nerve projections from the intra-parenchymal ganglia is associated with severe fatty infiltration.
CONCLUSIONS/INTERPRETATION: We present new perspectives of human pancreas and islet innervation via 3D histology. Our results strongly suggest that fatty infiltration in the human pancreas creates a neurotrophic microenvironment and promotes remodelling of pancreatic innervation.
目的/假设：在小鼠中鉴定出胰腺神经胰岛网络表明，类似的胰岛和神经整合可能存在于人类胰腺中。为了在临床相关环境中描述神经胰岛网络和胰内神经节，我们通过 3 维（3D）组织学检查了健康和脂肪浸润的人类胰腺，并将人类胰腺微环境与小鼠的对应物进行了比较。
使用来自正常 BMI、高 BMI（≥25）和 2 型糖尿病个体的人胰腺标本来研究神经胰岛网络。通过组织透明化制备透明标本，用于透射光和深部组织荧光成像，以同时可视化浸润的脂肪细胞、胰岛和神经血管网络。
高清晰度的人类胰岛图像显示，交感神经和副交感神经都进入胰岛核心，并存在于胰岛细胞的直接微环境中。在胰岛周围，通过 3D 组织学可以观察到神经胰岛网络，以识别胰内神经节（小叶间和小叶内神经节）和胰岛-神经节关联。在人类中，但不在小鼠中，胰腺脂肪浸润（BMI 依赖性）表现为脂肪细胞浸润到实质中，并在小叶间空间中积累，小叶间神经节也存在于该空间中。我们鉴定出在小叶间空间中形成的脂肪-神经节复合物和围绕脂肪细胞的神经节增大。在 2 型糖尿病患者的标本中，与严重脂肪浸润相关的是，来自小叶内神经节的神经投射数量增加。
结论/解释：我们通过 3D 组织学呈现了人类胰腺和胰岛神经支配的新视角。我们的结果强烈表明，人类胰腺中的脂肪浸润创造了一个神经营养微环境，并促进了胰腺神经支配的重塑。
