Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia.

中文翻译：

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胰岛 β 细胞产生的 NUCB2/nesfatin-1 维持胰岛素分泌和血糖，同时抑制 β 细胞中的 UCP-2。


Nesfatin-1 是一种由核结合素 2 (NUCB2) 加工而成的下丘脑厌食肽。 NUCB2/nesfatin-1 的中枢和外周给药可增强葡萄糖代谢和胰岛素释放。 NUCB2/nesfatin-1 也定位于胰岛，但其功能仍不清楚。为了探索胰腺 β 细胞产生的 NUCB2/nesfatin-1 的作用，我们开发了胰腺 β 细胞特异性 NUCB2 敲除 (βNUCB2 KO) 小鼠和 NUCB2 基因敲除 (shNUCB2) MIN6 β 细胞系。在 βNUCB2 KO 小鼠中，从 12 周龄开始，随意血糖升高。在12周的葡萄糖耐量试验中，禁食8小时的βNUCB2 KO小鼠在15分钟时胰岛素分泌减少，2小时血糖增加。在从 βNUCB2 KO 小鼠分离的胰岛中，高葡萄糖刺激的胰岛素分泌 (GSIS) 受损。在 shNUCB2 MIN6 细胞中，GSIS 降低，UCP-2 mRNA 表达升高。这些结果表明，GSIS 受损可能与 NUCB2 沉默的 β 细胞中 UCP-2 过度表达有关，表明 β 细胞产生的 NUCB2/nesfatin-1 维持 GSIS，从而维持血糖。