Human β-cell proliferation and intracellular signaling: part 3.
Human β-cell proliferation and intracellular signaling: part 3.
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DOI：
10.2337/db14-1843
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发表时间：
2015-06
期刊：
影响因子：
7.7
通讯作者：
Kulkarni RN
中科院分区：
文献类型：
--
作者：
Stewart AF;Hussain MA;García-Ocaña A;Vasavada RC;Bhushan A;Bernal-Mizrachi E;Kulkarni RN
这是与胰腺 β 细胞增殖相关的细胞内信号传导途径系列观点中的第三篇。我们将啮齿动物 β 细胞的庞大知识库与更有限的人类数据库进行了对比。随着 1 型糖尿病发病率的增加，以及人们认识到 2 型糖尿病部分是由于功能性 β 细胞缺乏所致，因此迫切需要找到扩大人类 β 细胞数量的治疗方法。治疗方法可能包括干细胞分化、转分化或尸体胰岛或残留内源性 β 细胞的扩增。在这些观点中，我们重点关注 β 细胞增殖。过去的观点回顾了基本的细胞周期调节及其上游调节，通过磷脂酰肌醇-3激酶/哺乳动物雷帕霉素信号传导靶点、葡萄糖、糖原合酶激酶-3和肝激酶B1、蛋白激酶Cze、钙-钙调磷酸酶-活化T细胞的核因子、表皮生长因子/血小板衍生生长因子家族成员、Wnt/β-连环蛋白、瘦素以及雌激素和黄体酮进行胰岛素/IGF信号传导。在这里，我们强调 Janus 激酶/信号转导器和转录激活剂、Ras/Raf/细胞外信号相关激酶、钙粘蛋白和整合素、G 蛋白偶联受体和转化生长因子 β 信号传导。我们希望这三个观点能够向新的研究人员介绍这些途径，并鼓励更多的研究人员集中精力了解如何利用关键的细胞内信号传导途径来治疗糖尿病的人类 β 细胞再生。
This is the third in a series of Perspectives on intracellular signaling pathways coupled to proliferation in pancreatic β-cells. We contrast the large knowledge base in rodent β-cells with the more limited human database. With the increasing incidence of type 1 diabetes and the recognition that type 2 diabetes is also due in part to a deficiency of functioning β-cells, there is great urgency to identify therapeutic approaches to expand human β-cell numbers. Therapeutic approaches might include stem cell differentiation, transdifferentiation, or expansion of cadaver islets or residual endogenous β-cells. In these Perspectives, we focus on β-cell proliferation. Past Perspectives reviewed fundamental cell cycle regulation and its upstream regulation by insulin/IGF signaling via phosphatidylinositol-3 kinase/mammalian target of rapamycin signaling, glucose, glycogen synthase kinase-3 and liver kinase B1, protein kinase Cζ, calcium-calcineurin–nuclear factor of activated T cells, epidermal growth factor/platelet-derived growth factor family members, Wnt/β-catenin, leptin, and estrogen and progesterone. Here, we emphasize Janus kinase/signal transducers and activators of transcription, Ras/Raf/extracellular signal–related kinase, cadherins and integrins, G-protein–coupled receptors, and transforming growth factor β signaling. We hope these three Perspectives will serve to introduce these pathways to new researchers and will encourage additional investigators to focus on understanding how to harness key intracellular signaling pathways for therapeutic human β-cell regeneration for diabetes.
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