Autocrine regulation of single pancreatic β-cell survival
Autocrine regulation of single pancreatic β-cell survival
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DOI：
10.2337/diabetes.53.8.2018
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发表时间：
2004-08-01
期刊：
影响因子：
7.7
通讯作者：
Hiriart, M
中科院分区：
文献类型：
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作者：
Navarro-Tableros, V;Sánchez-Soto, MC;Hiriart, M
细胞的功能和存活部分取决于生长因子的存在。我们探讨了胰岛素和神经生长因子（NGF）对成年大鼠胰腺p细胞存活和激素分泌的自分泌调节作用。当NGF或胰岛素信号通路在培养基中被阻断时，细胞存活率较对照组下降，细胞凋亡是细胞死亡的主要机制。为了进一步探讨葡萄糖在β细胞存活中的作用，我们将细胞在2.6 mmol/l葡萄糖中培养16 h，观察到近17%的细胞发生凋亡；这种作用被神经生长因子部分阻止，被胰岛素治疗几乎完全抑制。高K+浓度也有同样的效果，这表明细胞分泌的胰岛素和NGF对存活的影响负有责任，而不是葡萄糖本身。用NGF抗体或K252a阻断NGF信号传导可减少存活细胞的胰岛素生物合成和分泌。此外，胰岛素分泌率较高的功能性β细胞亚群更容易受到K252a的影响。这些结果进一步表明，NGF和胰岛素在胰腺β细胞存活和功能中发挥重要的自我调节作用，并强烈提示需要探索糖尿病治疗的新重点。
Function and survival of cells depend in part on the presence of growth factors. We explored the autocrine regulation of insulin and nerve growth factor (NGF) on single adult rat pancreatic P-cell survival and hormone secretion. When NGF or insulin signaling were blocked in culture media, cell survival decreased compared with control cells, with apoptosis being the main mechanism of cell death. To further explore the role of glucose in beta-cell survival, we cultured the cells for 16 h in 2.6 mmol/l glucose and observed that nearly 17% of the cells developed apoptosis; this effect was partially prevented by NGF and almost completely inhibited by insulin treatment. A high K+ concentration had the same effect, suggesting that insulin and NGF secretion by the cells was responsible for the survival effects and not glucose per se. Blocking NGF signaling with an NGF antibody or with K252a reduced insulin biosynthesis and secretion in the cells that survived the treatment. Moreover, the functional beta-cell subpopulation with a higher insulin secretion rate is more susceptible to K252a. These results further indicate that NGF and insulin play important autoregulatory roles in pancreatic beta-cell survival and function and strongly suggest the need to explore new focuses in diabetes treatment.