Diabetes results from insufficient numbers of functional pancreatic β-cells. Thus, increasing the number of available functional β-cells ex vivo for transplantation, or regenerating them in situ in diabetic patients, is a major focus of diabetes research. The transcription factor, Myc, discovered decades ago, lies at the nexus of most, if not all, known proliferative pathways. Based on this, many studies in the 1990’s and early 2000’s explored the potential of harnessing Myc expression to expand β-cells for diabetes treatment. Nearly all these studies in β-cells used pathophysiological or supraphysiological levels of Myc and reported enhanced β-cell death, de-differentiation or the formation of insulinomas if co-overexpressed with Bcl-xL, an inhibitor of apoptosis. This obviously reduced the enthusiasm for Myc as a therapeutic target for β-cell regeneration. However, recent studies indicate that “gentle” induction of Myc expression enhances β-cell replication without induction of cell death or loss of insulin secretion, suggesting that appropriate levels of Myc could have therapeutic potential for β-cell regeneration. Furthermore, although it has been known for decades that Myc is induced by glucose in β-cells very little is known about how this essential anabolic transcription factor perceives and responds to nutrients and increased insulin demand in vivo. Here we summarize the previous and recent knowledge of Myc in the β-cell, its potential for β-cell regeneration and its physiological importance for neonatal and adaptive β-cell expansion.

中文翻译：

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Myc 在胰腺 β 细胞中的多次生命


糖尿病是由功能性胰腺 β 细胞数量不足引起的。因此，增加可用于移植的离体功能性β细胞的数量，或在糖尿病患者体内原位再生它们，是糖尿病研究的主要焦点。几十年前发现的转录因子 Myc 位于大多数（如果不是全部）已知增殖途径的联系中。基于此，1990 年代和 2000 年代初的许多研究探索了利用 Myc 表达来扩增 β 细胞用于糖尿病治疗的潜力。几乎所有这些针对 β 细胞的研究都使用 Myc 的病理生理学或超生理学水平，并报告如果与细胞凋亡抑制剂 Bcl-xL 共过表达，β 细胞死亡、去分化或胰岛素瘤的形成会增强。这显然降低了人们对 Myc 作为 β 细胞再生治疗靶点的热情。然而，最近的研究表明，“温和”诱导 Myc 表达可增强 β 细胞复制，而不会诱导细胞死亡或胰岛素分泌丧失，这表明适当水平的 Myc 可能具有治疗 β 细胞再生的潜力。此外，尽管数十年来人们都知道 Myc 是由 β 细胞中的葡萄糖诱导的，但人们对这种重要的合成代谢转录因子如何感知和响应体内营养物质和增加的胰岛素需求却知之甚少。在这里，我们总结了 Myc 在 β 细胞中的先前和最新知识、其对 β 细胞再生的潜力及其对新生儿和适应性 β 细胞扩增的生理重要性。