Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation.
Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation.
复制标题
DOI：
10.1016/j.celrep.2013.06.019
复制
发表时间：
2013-07-25
期刊：
影响因子：
8.8
通讯作者：
Kuruvilla R
中科院分区：
文献类型：
--
作者：
Borden P;Houtz J;Leach SD;Kuruvilla R
交感神经元依赖于靶源性神经营养线索来控制其存活和生长。然而，交感神经支配是否有助于靶组织的发育尚不清楚。在这里，我们报告说，交感神经支配是必要的胰岛的形成和功能成熟。在发育过程中，交感神经支配的遗传或药理学消融导致小鼠胰岛结构改变，胰岛素分泌减少和葡萄糖耐量受损。在β-肾上腺素能信号传导的药理学阻断中观察到类似的缺陷。相反，给予β-肾上腺素能激动剂恢复了去神经支配动物的胰岛形态和葡萄糖耐量。此外，在神经元-胰岛共培养物中，交感神经元以β-肾上腺素能依赖的方式促进胰岛细胞迁移。这项研究表明，胰岛结构需要来自邻近组织（如交感神经）的外在诱导线索，并表明交感神经支配的早期扰动可能是代谢紊乱的基础。
Sympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in de-innervated animals. Furthermore, in neuron-islet co-cultures, sympathetic neurons promoted islet cell migration in a β-adrenergic dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves, and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders.
登录
查看更多内容
DOI：
10.1083/jcb.144.2.325
发表时间：
1999-01-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Esni F;Täljedal IB;Perl AK;Cremer H;Christofori G;Semb H
通讯作者：
Semb H
影响因子：
2.9
作者：
DUMM, CLAG;SEMINO, MC;GAGLIARDINO, JJ
通讯作者：
GAGLIARDINO, JJ
影响因子：
4.8
作者：
HOPCROFT, DW;MASON, DR;SCOTT, RS
通讯作者：
SCOTT, RS
影响因子：
8.2
作者：
Chiu, Y. -C.;Hua, T. -E.;Tang, S. -C.
通讯作者：
Tang, S. -C.
DOI：
10.1152/ajpendo.00321.2002
发表时间：
2003-01-01
影响因子：
5.1
作者：
Hara, M;Wang, XY;Bell, GI
通讯作者：
Bell, GI