How does glucagon-like peptide 1 stimulate human β-cell proliferation? A lesson from islet graft experiments.
How does glucagon-like peptide 1 stimulate human β-cell proliferation? A lesson from islet graft experiments.
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DOI：
10.1111/jdi.12861
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发表时间：
2018-11
影响因子：
3.2
通讯作者：
Fujitani Y
中科院分区：
文献类型：
--
作者：
Fujitani Y
2型糖尿病的发病率随着年龄的增长而增加。功能β细胞质量的年龄依赖性下降有助于增加糖尿病发病的风险，反映了胰腺β细胞在葡萄糖稳态中的核心作用。事实上，已知人类和啮齿动物β细胞的复制率随着年龄的增长而急剧下降，β细胞的这种特征可能解释了老年人群中2型糖尿病发病增加的原因。β细胞增殖年龄依赖性下降的分子机制已被广泛研究，主要使用啮齿动物和体外培养系统，但其分子基础仍在很大程度上未知。最近，一项将人胰岛移植到免疫缺陷小鼠体内的研究表明，胰高血糖素样肽1受体激活仅在有限的时间窗内诱导人β细胞增殖的机制。作者发现，exendin‐4的有丝分裂作用需要活化T细胞信号传导的钙调磷酸酶/核因子，并且仅在幼年胰岛中，exendin‐4诱导活化T细胞信号传导成分的核因子的表达，以及促进β细胞增殖的下游靶基因。这些发现为为什么胰高血糖素样肽1仅在幼年人β细胞中发挥有丝分裂作用提供了机制解释。
The incidence of type 2 diabetes increases with age. The age‐dependent decline in functional β‐cell mass contributes to the increased risk of onset of diabetes, reflecting the central role of pancreatic β‐cells in glucose homeostasis. Indeed, the replication rate of human and rodent β‐cells is known to decline sharply with age, and such a characteristic of β‐cells might explain the increased onset of type 2 diabetes in the older population. The molecular mechanism involved in the age‐dependent decline of β‐cell proliferation has been extensively studied, mainly using rodents and in vitro culture systems, but its molecular basis is still largely unknown. A mechanism by which glucagon‐like peptide‐1 receptor activation induces human β‐cell proliferation only within a restricted time window was recently suggested in a study in which human islets were grafted into immunodeficient mice. The authors found that the mitogenic effects of exendin‐4 require calcineurin/nuclear factor of activated T‐cells signaling, and that only in juvenile islets, exendin‐4 induced the expression of nuclear factor of activated T‐cells signaling components, as well as downstream target genes that facilitate β‐cell proliferation. These findings provide a mechanistic explanation as to why glucagon‐like peptide 1 exerts mitogenic effects only in juvenile human β‐cells.
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影响因子：
3.6
作者：
Oetjen, E;Baun, D;Knepel, W
通讯作者：
Knepel, W
影响因子：
15.9
作者：
Dai, Chunhua;Hang, Yan;Powers, Alvin C.
通讯作者：
Powers, Alvin C.
影响因子：
11.8
作者：
Goodyer, William R.;Gu, Xueying;Liu, Yinghua;Bottino, Rita;Crabtree, Gerald R.;Kim, Seung K.
通讯作者：
Kim, Seung K.
DOI：
10.1016/j.bbrc.2009.10.054
发表时间：
2009-12-18
影响因子：
3.1
作者：
Arakawa, Masayuki;Ebato, Chie;Watada, Hirotaka
通讯作者：
Watada, Hirotaka