Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.
Department of Biomedical Engineering, College of Engineering, University of Florida, Gainesville, FL, 32610, USA.
Sci Rep. 2021 Mar 22;11(1):6562. doi: 10.1038/s41598-021-85659-8.
Dysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac β-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.
1 型糖尿病（T1D）中胰高血糖素分泌失调涉及餐后高分泌，但低血糖时分泌不足。交感神经系统调节胰高血糖素分泌。为了研究 T1D 中的胰岛交感神经支配，分析了对照非糖尿病器官供体、非糖尿病胰岛自身抗体阳性个体（AAb）和年龄匹配的 T1D 患者中的交感酪氨酸羟化酶（TH）轴突。与 T1D 相比，AAb 中的胰岛 TH 轴突数量和密度显著减少，而各组之间外分泌 TH 轴突体积或长度无显著差异。在长期患有糖尿病的 T1D 个体中，TH 轴突与胰岛 α 细胞非常接近。胰岛 RNA 测序和 qRT-PCR 分析鉴定出去甲肾上腺素降解、α-肾上腺素能信号、心脏β-肾上腺素能信号、儿茶酚胺生物合成和其他神经病理学途径的显著改变。TH 轴突与胰岛 α 细胞的接近支持了交感传出神经元直接调节胰高血糖素分泌的模型。交感神经胰岛支配和内在肾上腺素能信号通路可能是改善 T1D 中胰高血糖素分泌的新靶点。
