van der Meulen Talitha, Huising Mark O
Department of NeurobiologyPhysiology and Behavior, College of Biological SciencesDepartment of Physiology and Membrane BiologySchool of Medicine, University of California, 193 Briggs Hall, One Shields Avenue, Davis, California 95616, USA.
Department of NeurobiologyPhysiology and Behavior, College of Biological SciencesDepartment of Physiology and Membrane BiologySchool of Medicine, University of California, 193 Briggs Hall, One Shields Avenue, Davis, California 95616, USA Department of NeurobiologyPhysiology and Behavior, College of Biological SciencesDepartment of Physiology and Membrane BiologySchool of Medicine, University of California, 193 Briggs Hall, One Shields Avenue, Davis, California 95616, USA
J Mol Endocrinol. 2015 Apr;54(2):R103-17. doi: 10.1530/JME-14-0290.
The α and β cells act in concert to maintain blood glucose. The α cells release glucagon in response to low levels of glucose to stimulate glycogenolysis in the liver. In contrast, β cells release insulin in response to elevated levels of glucose to stimulate peripheral glucose disposal. Despite these opposing roles in glucose homeostasis, α and β cells are derived from a common progenitor and share many proteins important for glucose sensing and hormone secretion. Results from recent work have underlined these similarities between the two cell types by revealing that β-to-α as well as α-to-β transdifferentiation can take place under certain experimental circumstances. These exciting findings highlight unexpected plasticity of adult islets and offer hope of novel therapeutic paths to replenish β cells in diabetes. In this review, we focus on the transcription factor networks that establish and maintain pancreatic endocrine cell identity and how they may be perturbed to facilitate transdifferentiation.
α细胞和β细胞协同作用以维持血糖水平。α细胞在血糖水平较低时释放胰高血糖素，以刺激肝脏中的糖原分解。相反，β细胞在血糖水平升高时释放胰岛素，以刺激外周组织对葡萄糖的利用。尽管在葡萄糖稳态中发挥着相反的作用，但α细胞和β细胞源自共同的祖细胞，并共享许多对葡萄糖感知和激素分泌至关重要的蛋白质。最近的研究结果表明，在某些实验条件下，β细胞可以转分化为α细胞，α细胞也可以转分化为β细胞，这突显了这两种细胞类型之间的这些相似性。这些令人兴奋的发现突出了成年胰岛意想不到的可塑性，并为糖尿病中补充β细胞提供了新的治疗途径的希望。在这篇综述中，我们重点关注建立和维持胰腺内分泌细胞身份的转录因子网络，以及如何扰动这些网络以促进转分化。
