Insulin-producing β-cells in pancreatic islets are regulated by systemic cues and, locally, by adjacent islet hormone-producing ‘non-β-cells’ (namely α-cells, δ-cells and γ-cells). Yet whether the non-β-cells are required for accurate insulin secretion is unclear. Here, we studied mice in which adult islets are exclusively composed of β-cells and human pseudoislets containing only primary β-cells. Mice lacking non-β-cells had optimal blood glucose regulation, enhanced glucose tolerance, insulin sensitivity and restricted body weight gain under a high-fat diet. The insulin secretion dynamics in islets composed of only β-cells was comparable to that in intact islets. Similarly, human β-cell pseudoislets retained the glucose-regulated mitochondrial respiration, insulin secretion and exendin-4 responses of entire islets. The findings indicate that non-β-cells are dispensable for blood glucose homeostasis and β-cell function. These results support efforts aimed at developing diabetes treatments by generating β-like clusters devoid of non-β-cells, such as from pluripotent stem cells differentiated in vitro or by reprograming non-β-cells into insulin producers in situ.

胰岛中产生胰岛素的 β 细胞受到全身信号的调节，并且局部受到邻近胰岛激素产生的“非 β 细胞”（即 α 细胞、δ 细胞和 γ 细胞）的调节。然而，准确的胰岛素分泌是否需要非β细胞尚不清楚。在这里，我们研究了成年胰岛完全由 β 细胞组成的小鼠和仅含有初级 β 细胞的人类伪胰岛。缺乏非β细胞的小鼠在高脂肪饮食下具有最佳的血糖调节、增强的葡萄糖耐量、胰岛素敏感性和有限的体重增加。仅由 β 细胞组成的胰岛中的胰岛素分泌动态与完整胰岛中的胰岛素分泌动态相当。同样，人类 β 细胞伪胰岛保留了整个胰岛的葡萄糖调节的线粒体呼吸、胰岛素分泌和 exendin-4 反应。研究结果表明，非β细胞对于血糖稳态和β细胞功能来说是可有可无的。这些结果支持了旨在通过产生不含非β细胞的β样簇来开发糖尿病治疗方法的努力，例如从体外分化的多能干细胞或通过将非β细胞原位重编程为胰岛素生产者。