Ablation of somatostatin cells leads to impaired pancreatic islet function and neonatal death in rodents.
Ablation of somatostatin cells leads to impaired pancreatic islet function and neonatal death in rodents.
复制标题
生长抑素细胞的消融会导致啮齿动物胰岛功能受损和新生儿死亡
DOI：
10.1038/s41419-018-0741-4
复制
发表时间：
2018-06-07
影响因子：
9
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Li N;Yang Z;Li Q;Yu Z;Chen X;Li JC;Li B;Ning SL;Cui M;Sun JP;Yu X
哺乳动物的生长抑素（SST）分泌细胞主要分布在胰岛、脑、胃和肠中，具有多种生理功能。特别是分泌sst的δ细胞是朗格汉斯胰岛中第三常见的细胞类型。最近的研究表明，胰腺δ细胞和β细胞之间的旁分泌相互作用失调导致葡萄糖稳态受损，并有助于糖尿病的发展。然而，关于SST细胞在葡萄糖稳态控制中的功能重要性的直接证据仍然缺乏。在本研究中，我们通过将Sst-cre转基因小鼠与R26DTA小鼠（SstCre R26DTA）杂交，特异性消融sst分泌细胞。sstre R26DTA小鼠出现新生儿死亡。这些严重低血糖小鼠的寿命通过补充葡萄糖延长。此外，我们观察到SST细胞缺乏导致胰岛素含量增加和胰岛素释放过度，这可能导致观察到的低血糖。出乎意料的是，尽管SST对胰岛素含量的调节至关重要，但胰腺δ细胞通过内源性促肾上腺皮质激素释放激素受体2 （CRHR2）活性产生的SST以外的其他因子在维持正常胰岛素释放和新生儿静息状态下的葡萄糖稳态中起主要作用。综上所述，我们的研究结果表明，新生小鼠的SST细胞在控制胰岛素释放和正常胰岛功能方面发挥了关键作用。此外，我们提供了直接的体内证据，证明SST细胞的功能重要性，它对新生儿的生存和葡萄糖稳态的维持至关重要。
The somatostatin (SST)-secreting cells were mainly distributed in the pancreatic islets, brain, stomach and intestine in mammals and have many physiological functions. In particular, the SST-secreting δ cell is the third most common cell type in the islets of Langerhans. Recent studies have suggested that dysregulation of paracrine interaction between the pancreatic δ cells and β cells results in impaired glucose homeostasis and contributes to diabetes development. However, direct evidence of the functional importance of SST cells in glucose homeostasis control is still lacking. In the present study, we specifically ablated SST-secreting cells by crossing Sst-cre transgenic mice with R26DTA mice (SstCre R26DTA). The SstCre R26DTA mice exhibited neonatal death. The life spans of these mice with severe hypoglycemia were extended by glucose supplementation. Moreover, we observed that SST cells deficiency led to increased insulin content and excessive insulin release, which might contribute to the observed hypoglycemia. Unexpectedly, although SST is critical for the regulation of insulin content, factors other than SST that are produced by pancreatic δ cells via their endogenous corticotropin-releasing hormone receptor 2 (CRHR2) activity play the main roles in maintaining normal insulin release, as well as neonatal glucose homeostasis in the resting state. Taken together, our results identified that the SST cells in neonatal mouse played critical role in control of insulin release and normal islet function. Moreover, we provided direct in vivo evidence of the functional importance of the SST cells, which are essential for neonatal survival and the maintenance of glucose homeostasis.
登录
查看更多内容
抑制蛋白偏向的 AT1R 激动作用通过 TRPC3 偶联诱导急性儿茶酚胺分泌
影响因子：
16.6
作者：
Liu CH;Gong Z;Liang ZL;Liu ZX;Yang F;Sun YJ;Ma ML;Wang YJ;Ji CR;Wang YH;Wang MJ;Cui FA;Lin A;Zheng WS;He DF;Qu CX;Xiao P;Liu CY;Thomsen AR;Joseph Cahill T 3rd;Kahsai AW;Yi F;Xiao KH;Xue T;Zhou Z;Yu X;Sun JP
通讯作者：
Sun JP
DOI：
10.1152/ajpendo.00207.2012
发表时间：
2012-11-01
影响因子：
5.1
作者：
Kailey, Balrik;van de Bunt, Martijn;Braun, Matthias
通讯作者：
Braun, Matthias
影响因子：
8.1
作者：
DiGruccio MR;Mawla AM;Donaldson CJ;Noguchi GM;Vaughan J;Cowing-Zitron C;van der Meulen T;Huising MO
通讯作者：
Huising MO
影响因子：
10.5
作者：
Collombat, P;Mansouri, A;Gruss, P
通讯作者：
Gruss, P
影响因子：
7.7
作者：
Franklin, I;Gromada, J;Wollheim, CB
通讯作者：
Wollheim, CB