Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats
Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats
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DOI：
10.2337/diabetes.51.10.2997
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Taborsky, GJ
中科院分区：
文献类型：
--
作者：
Mei, Q;Mundinger, TO;Taborsky, GJ
为了发现胰岛交感神经是否在胰岛B细胞的自身免疫破坏过程中受损，我们使用针对囊泡单胺转运体2（VMAT 2）（交感神经末梢的标记物）的抗体对来自生物育种（BB）糖尿病大鼠的胰腺切片进行免疫染色。我们发现，与非糖尿病对照组相比，糖尿病仅1-2周的BB大鼠胰岛中VMAT 2阳性纤维面积显著减少。相反，在这些早期糖尿病BB大鼠中，外分泌胰腺中的VMAT 2阳性纤维面积没有显著减少。此外，与对照组相比，链脲佐菌素糖尿病大鼠的胰岛中VMAT 2阳性纤维面积没有减少。最终在心脏中发生的经典糖尿病自主神经病变（DAN）在该早期阶段不存在于BB糖尿病大鼠中，如通过正常心脏VMAT 2免疫染色和正常心脏去甲肾上腺素含量所证明的。此外，与DAN相反，这种胰岛神经病变并没有随着糖尿病的持续时间而恶化。这些数据提供了迄今未被认识的早期交感神经胰岛神经病（eSIN）的证据。由于eSIN选择性地发生在胰岛中，发病迅速，并且与自身免疫性糖尿病相关，但与化学诱导的糖尿病无关，因此它在位置、时间过程和机制上与DAN不同。
To discover whether islet sympathetic nerves are damaged during the autoimmune destruction of islet B-cells, we immunostained sections of pancreas from Bio-Breeder (BB) diabetic rats, using antibodies against vesicular monoamine transporter 2 (VMAT2), a marker of sympathetic nerve terminals. We found a marked decrease in the VMAT2-positive fiber area in the islets of BB rats that had been diabetic for only 1-2 weeks compared with their nondiabetic controls. In contrast, there was no significant decrease in the VMAT2-positive fiber area in the exocrine pancreas in these early diabetic BB rats. Furthermore, streptozotocin-diabetic rats showed no decrease in VMAT2-positive fiber area in their islets compared with controls. The classical diabetic autonomic neuropathy (DAN) that eventually occurs in the heart was not present in BB diabetic rats at this early stage as evidenced by normal cardiac VMAT2 immunostaining and normal cardiac norepinephrine content. Also, in contrast to DAN, this islet neuropathy did not worsen with duration of diabetes. These data provide evidence of a heretofore unrecognized early sympathetic islet neuropathy (eSIN). Because eSIN occurs selectively in the islet, is rapid in onset, and is associated with autoimmune but not chemically induced diabetes, it is distinct from DAN in location, time course, and mechanism.